Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	3.9	5.2	2013	15.3 Days	CHF 2600
Current Issues in Molecular Biology cimb	2.8	2.9	1999	16.8 Days	CHF 2200
International Journal of Molecular Sciences ijms	4.9	8.1	2000	18.1 Days	CHF 2900
Life life	3.2	4.3	2011	18 Days	CHF 2600
Physiologia physiologia	-	-	2021	27.9 Days	CHF 1000

16 pages, 1326 KiB

Open AccessArticle

Acute Spontaneous Lobar Cerebral Hemorrhages Present a Different Clinical Profile and a More Severe Early Prognosis than Deep Subcortical Intracerebral Hemorrhages—A Hospital-Based Stroke Registry Study

by Joana Maria Flaquer-Pérez de Mendiola, Adrià Arboix, Luís García-Eroles and Maria José Sánchez-López

Biomedicines 2023, 11(1), 223; https://doi.org/10.3390/biomedicines11010223 - 16 Jan 2023

Cited by 20 | Viewed by 4289

Abstract

Acute spontaneous intracerebral hemorrhage (ICH) is the most severe stroke subtype, with a high risk of death, dependence, and dementia. Knowledge about the clinical profile and early outcomes of ICH patients with lobar versus deep subcortical brain topography remains limited. In this study, [...] Read more.

Acute spontaneous intracerebral hemorrhage (ICH) is the most severe stroke subtype, with a high risk of death, dependence, and dementia. Knowledge about the clinical profile and early outcomes of ICH patients with lobar versus deep subcortical brain topography remains limited. In this study, we investigated the effects of ICH topography on demographics, cerebrovascular risk factors, clinical characteristics, and early outcomes in a sample of 298 consecutive acute ICH patients (165 with lobar and 133 with subcortical hemorrhagic stroke) available in a single-center-based stroke registry over 24 years. The multiple logistic regression analysis shows that variables independently associated with lobar ICH were early seizures (OR 6.81, CI 95% 1.27–5.15), chronic liver disease (OR 4.55, 95% CI 1.03–20.15), hemianopia (OR 2.55, 95% CI 1.26–5.15), headaches (OR 1.90, 95% CI 1.90, 95% IC 1.06–3.41), alcohol abuse (>80 gr/day) (OR 0–10, 95% CI 0.02–0,53), hypertension (OR 0,41, 95% CI 0.23–0–70), sensory deficit (OR 0.43, 95% CI 0.25–0.75), and limb weakness (OR: 0.47, 95% CI 0.24–0.93). The in-hospital mortality was 26.7% for lobar and 16.5% for subcortical ICH. The study confirmed that the clinical spectrum, prognosis, and early mortality of patients with ICH depend on the site of bleeding, with a more severe early prognosis in lobar intracerebral hemorrhage. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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11 pages, 1991 KiB

Open AccessArticle

Exendin-4 Increases Scavenger Receptor Class BI Expression via Activation of AMPK/FoxO1 in Human Vascular Endothelial Cells

by Jingya Lyu, Hitomi Imachi, Kensaku Fukunaga, Seisuke Sato, Toshihiro Kobayashi, Takanobu Saheki, Salimah Japar, Hisakazu Iwama, Yuta Matsumura, Miyo Ozaki, Takafumi Yoshimura and Koji Murao

Curr. Issues Mol. Biol. 2022, 44(11), 5474-5484; https://doi.org/10.3390/cimb44110370 - 3 Nov 2022

Cited by 4 | Viewed by 1858

Abstract

Glucagon-like peptide-1 receptor agonist (GLP-1RA) has been clinically proven to protect endothelial function. Previously, we demonstrated that endothelial NO synthase (eNOS) was activated by high-density lipoprotein (HDL) via its scavenger receptor of the B class/human homologue of SR-BI, CD36 and LIMPII analogous-1(hSR-BI/CLA-1). Here, [...] Read more.

Glucagon-like peptide-1 receptor agonist (GLP-1RA) has been clinically proven to protect endothelial function. Previously, we demonstrated that endothelial NO synthase (eNOS) was activated by high-density lipoprotein (HDL) via its scavenger receptor of the B class/human homologue of SR-BI, CD36 and LIMPII analogous-1(hSR-BI/CLA-1). Here, we investigated the effect of GLP-1RA and exendin-4 on the expression of hSR-BI/CLA-1 in HUVECs. Our results confirmed that GLP-1R was expressed in HUVECs by PCR and exendin-4 significantly enhanced HDL-induced eNOS activation. Next, exendin-4 increased the expression of hSR-BI/CLA-1 and a blockade of GLP-1R cancelled this effect. Further, the hSR-BI/CLA-1 transcriptional activity was enhanced by exendin-4, which was diminished by the inhibition of AMPK or dominant-negative AMPK-α-subunit. Moreover, AMPK was phosphorylated by the activation of GLP-1R. Next, ChIP assay demonstrated that exendin-4 increased the FoxO1-binding in the hSR-BI/CLA-1 promoter by upregulation of FoxO1. Mutation of FoxO1-binding or silencing of FoxO1 cancelled the effect of exendin-4 on hSR-BI/CLA-1 expression. Exendin-4 reduced FoxO1 phosphorylation and induced its nuclear accumulation, while this effect was altered by the blocking of GLP-1R or inhibition of AMPK pathway. In summary, our results proved that exendin-4 increased hSR-BI/CLA-1 expression via the AMPK/FoxO1 pathway to activate eNOS, providing a basic mechanism underlining the protective effect of GLP-1RA on endothelial function. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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16 pages, 1980 KiB

Open AccessArticle

The Accelerated Progression of Atherosclerosis Correlates with Decreased miR-33a and miR-21 and Increased miR-122 and miR-3064-5p in Circulation and the Liver of ApoE-/- Mice with Streptozocin (STZ)-Induced Type 2 Diabetes

by Hui-Yu Luo, Gan Li, Yu-Guo Liu, Yuan-Hao Wei, Jun-Bin Chen, Xiang-Fu Gu, Jia-Qi Tang, Yue Zhao, Chu-Hong Su, Ling-Yu Xiao, Fei Xiong, Zhong-Daixi Zheng, Shi-Ying Wang and Long-Ying Zha

Curr. Issues Mol. Biol. 2022, 44(10), 4822-4837; https://doi.org/10.3390/cimb44100328 - 13 Oct 2022

Cited by 4 | Viewed by 2379

Abstract

Atherosclerosis is a major risk factor for type 2 diabetes (T2D) mortality. We aim to investigate the changes in miR-21, miR-122, miR-33a and miR-3064-5p in circulation and the liver of ApoE-/- mice with streptozocin (STZ)-induced T2D. Twenty 5-week-old male ApoE-/- mice were randomly [...] Read more.

Atherosclerosis is a major risk factor for type 2 diabetes (T2D) mortality. We aim to investigate the changes in miR-21, miR-122, miR-33a and miR-3064-5p in circulation and the liver of ApoE-/- mice with streptozocin (STZ)-induced T2D. Twenty 5-week-old male ApoE-/- mice were randomly assigned to the control (n = 10) and T2D group (n = 10) and intraperitoneally injected with a citrate buffer and streptozotocin (STZ) (40 mg/kg BW) once a day for three consecutive days. The successfully STZ-induced T2D mice (n = 5) and control mice (n = 5) were then fed with a high-fat diet (HFD) for 34 weeks. Compared to the control mice, ApoE-/- mice with STZ-induced T2D had slower (p < 0.05) growth, increased (p < 0.05) total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), decreased (p < 0.05) high-density lipoprotein cholesterol (HDL-C) in serum, reduced (p < 0.05) TC and sterol regulatory element-binding protein-2 (Srebp-2), elevated (p < 0.05) ATP-binding-cassette-transporter-A1 (Abca1) in the liver, aggravated (p < 0.05) atherosclerotic lesions in the aorta, downregulated (p < 0.05) miR-21 and miR-33a, and upregulated (p < 0.05) miR-122 and miR-3064-5p in serum and the liver. In addition, the aortic lesions showed a positive correlation with miR-122 (r = 1.000, p = 0.001) and a negative correlation with miR-21 (r = −1.000, p = 0.001) in ApoE-/- mice with T2D. In conclusion, T2D-accelerated atherosclerosis correlates with a reduction in miR-21 and miR-33a and an elevation in miR-122 and miR-3064-5p in circulation and the liver of ApoE-/- mice. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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25 pages, 17065 KiB

Open AccessReview

Classical Angiogenic Signaling Pathways and Novel Anti-Angiogenic Strategies for Colorectal Cancer

by Mengyuan Cao, Yunmeng Wang, Guige Lu, Haoran Qi, Peiyu Li, Xiaoshuo Dai and Jing Lu

Curr. Issues Mol. Biol. 2022, 44(10), 4447-4471; https://doi.org/10.3390/cimb44100305 - 26 Sep 2022

Cited by 9 | Viewed by 4280

Abstract

Although productive progress has been made in colorectal cancer (CRC) researchs, CRC is the second most frequent type of malignancy and the major cause of cancer-related death among gastrointestinal cancers. As angiogenesis constitutes an important point in the control of CRC progression and [...] Read more.

Although productive progress has been made in colorectal cancer (CRC) researchs, CRC is the second most frequent type of malignancy and the major cause of cancer-related death among gastrointestinal cancers. As angiogenesis constitutes an important point in the control of CRC progression and metastasis, understanding the key signaling pathways that regulate CRC angiogenesis is critical in elucidating ways to inhibit CRC. Herein, we comprehensively summarized the angiogenesis-related pathways of CRC, including vascular endothelial growth factor (VEGF), nuclear factor-kappa B (NF-κB), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), Wingless and int-1 (Wnt), and Notch signaling pathways. We divided the factors influencing the specific pathway into promoters and inhibitors. Among these, some drugs or natural compounds that have antiangiogenic effects were emphasized. Furthermore, the interactions of these pathways in angiogenesis were discussed. The current review provides a comprehensive overview of the key signaling pathways that are involved in the angiogenesis of CRC and contributes to the new anti-angiogenic strategies for CRC. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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21 pages, 4753 KiB

Open AccessReview

Interplay between Artificial Intelligence and Biomechanics Modeling in the Cardiovascular Disease Prediction

by Xiaoyin Li, Xiao Liu, Xiaoyan Deng and Yubo Fan

Biomedicines 2022, 10(9), 2157; https://doi.org/10.3390/biomedicines10092157 - 1 Sep 2022

Cited by 10 | Viewed by 4371

Abstract

Cardiovascular disease (CVD) is the most common cause of morbidity and mortality worldwide, and early accurate diagnosis is the key point for improving and optimizing the prognosis of CVD. Recent progress in artificial intelligence (AI), especially machine learning (ML) technology, makes it possible [...] Read more.

Cardiovascular disease (CVD) is the most common cause of morbidity and mortality worldwide, and early accurate diagnosis is the key point for improving and optimizing the prognosis of CVD. Recent progress in artificial intelligence (AI), especially machine learning (ML) technology, makes it possible to predict CVD. In this review, we first briefly introduced the overview development of artificial intelligence. Then we summarized some ML applications in cardiovascular diseases, including ML−based models to directly predict CVD based on risk factors or medical imaging findings and the ML−based hemodynamics with vascular geometries, equations, and methods for indirect assessment of CVD. We also discussed case studies where ML could be used as the surrogate for computational fluid dynamics in data−driven models and physics−driven models. ML models could be a surrogate for computational fluid dynamics, accelerate the process of disease prediction, and reduce manual intervention. Lastly, we briefly summarized the research difficulties and prospected the future development of AI technology in cardiovascular diseases. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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20 pages, 1964 KiB

Open AccessReview

Topical Reappraisal of Molecular Pharmacological Approaches to Endothelial Dysfunction in Diabetes Mellitus Angiopathy

by Constantin Munteanu, Mariana Rotariu, Marius-Alexandru Turnea, Aurelian Anghelescu, Irina Albadi, Gabriela Dogaru, Sînziana Calina Silișteanu, Elena Valentina Ionescu, Florentina Carmen Firan, Anca Mirela Ionescu, Carmen Oprea and Gelu Onose

Curr. Issues Mol. Biol. 2022, 44(8), 3378-3397; https://doi.org/10.3390/cimb44080233 - 28 Jul 2022

Cited by 20 | Viewed by 3095

Abstract

Diabetes mellitus (DM) is a frequent medical problem, affecting more than 4% of the population in most countries. In the context of diabetes, the vascular endothelium can play a crucial pathophysiological role. If a healthy endothelium—which is a dynamic endocrine organ with autocrine [...] Read more.

Diabetes mellitus (DM) is a frequent medical problem, affecting more than 4% of the population in most countries. In the context of diabetes, the vascular endothelium can play a crucial pathophysiological role. If a healthy endothelium—which is a dynamic endocrine organ with autocrine and paracrine activity—regulates vascular tone and permeability and assures a proper balance between coagulation and fibrinolysis, and vasodilation and vasoconstriction, then, in contrast, a dysfunctional endothelium has received increasing attention as a potential contributor to the pathogenesis of vascular disease in diabetes. Hyperglycemia is indicated to be the major causative factor in the development of endothelial dysfunction. Furthermore, many shreds of evidence suggest that the progression of insulin resistance in type 2 diabetes is parallel to the advancement of endothelial dysfunction in atherosclerosis. To present the state-of-the-art data regarding endothelial dysfunction in diabetic micro- and macroangiopathy, we constructed this literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We interrogated five medical databases: Elsevier, PubMed, PMC, PEDro, and ISI Web of Science. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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17 pages, 799 KiB

Open AccessArticle

Association of Single Nucleotide Polymorphisms from Angiogenesis-Related Genes, ANGPT2, TLR2 and TLR9, with Spontaneous Preterm Labor

by Wioletta Izabela Wujcicka, Marian Kacerovsky, Adrian Krygier, Michał Krekora, Piotr Kaczmarek and Mariusz Grzesiak

Curr. Issues Mol. Biol. 2022, 44(7), 2939-2955; https://doi.org/10.3390/cimb44070203 - 30 Jun 2022

Cited by 2 | Viewed by 2684

Abstract

In this study, we hypothesized that the changes localized at angiopoietin-2 (ANGPT2), granulocyte-macrophage colony-stimulating factor (CSF2), fms-related tyrosine kinase 1 (FLT1) and toll-like receptor (TLR) 2, TLR6 and TLR9 genes were associated with spontaneous [...] Read more.

In this study, we hypothesized that the changes localized at angiopoietin-2 (ANGPT2), granulocyte-macrophage colony-stimulating factor (CSF2), fms-related tyrosine kinase 1 (FLT1) and toll-like receptor (TLR) 2, TLR6 and TLR9 genes were associated with spontaneous preterm labor (PTL), as well as with possible genetic alterations on PTL-related coagulation. This case-control genetic association study aimed to identify single nucleotide polymorphisms (SNPs) for the aforementioned genes, which are correlated with genetic risk or protection against PTL in Polish women. The study was conducted in 320 patients treated between 2016 and 2020, including 160 women with PTL and 160 term controls in labor. We found that ANGPT2 rs3020221 AA homozygotes were significantly less common in PTL cases than in controls, especially after adjusting for activated partial thromboplastin time (APTT) and platelet (PLT) parameters. TC heterozygotes for TLR2 rs3804099 were associated with PTL after correcting for anemia, vaginal bleeding, and history of threatened miscarriage or PTL. TC and CC genotypes in TLR9 rs187084 were significantly less common in women with PTL, compared to the controls, after adjusting for bleeding and gestational diabetes. For the first time, it was shown that three polymorphisms—ANGPT2 rs3020221, TLR2 rs3804099 and TLR9 rs187084 —were significantly associated with PTL, adjusted by pregnancy development influencing factors. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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7 pages, 658 KiB

Open AccessBrief Report

Procoagulant Activity in Amniotic Fluid Is Associated with Fetal-Derived Extracellular Vesicles

by Kirill R. Butov, Natalia A. Karetnikova, Dmitry Y. Pershin, Dmitry Y. Trofimov and Mikhail A. Panteleev

Curr. Issues Mol. Biol. 2022, 44(6), 2710-2716; https://doi.org/10.3390/cimb44060185 - 13 Jun 2022

Cited by 1 | Viewed by 2141

Abstract

Procoagulant activity in amniotic fluid (AF) is positively correlated with phosphatidylserine (PS) and tissue factor (TF)-expressing(+) extracellular vesicles (EVs). However, it is unknown if pathological fetal conditions may affect the composition, phenotype, and procoagulant potency of EVs in AF. We sought to evaluate [...] Read more.

Procoagulant activity in amniotic fluid (AF) is positively correlated with phosphatidylserine (PS) and tissue factor (TF)-expressing(+) extracellular vesicles (EVs). However, it is unknown if pathological fetal conditions may affect the composition, phenotype, and procoagulant potency of EVs in AF. We sought to evaluate EV-dependent procoagulant activity in AF from pregnant people with fetuses with or without diagnosed chromosomal mutations. AF samples were collected by transabdominal amniocentesis and assessed for common karyotype defects (total n = 11, 7 healthy and 4 abnormal karyotypes). The procoagulant activity of AF was tested using a fibrin generation assay with normal pooled plasma and plasmas deficient in factors XII, XI, IX, X, V, and VII. EV number and phenotype were determined by flow cytometry with anti-CD24 and anti-TF antibodies. We report that factor-VII-, X-, or V-deficient plasmas did not form fibrin clots in the presence of AF. Clotting time was significantly attenuated in AF samples with chromosomal mutations. In addition, CD24+, TF+, and CD24+ TF+ EV counts were significantly lower in this group. Finally, we found a significant correlation between EV counts and the clotting time induced by AF. In conclusion, we show that AF samples with chromosomal mutations had fewer fetal-derived CD24-bearing and TF-bearing EVs, which resulted in diminished procoagulant potency. This suggests that fetal-derived EVs are the predominant source of procoagulant activity in AF. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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18 pages, 972 KiB

Open AccessReview

The Pathological Links between Adiposity and the Carpal Tunnel Syndrome

by Marina Ruxandra Otelea, Roxana Nartea, Florina Georgeta Popescu, Anatoli Covaleov, Brindusa Ilinca Mitoiu and Adriana Sarah Nica

Curr. Issues Mol. Biol. 2022, 44(6), 2646-2663; https://doi.org/10.3390/cimb44060181 - 8 Jun 2022

Cited by 11 | Viewed by 4256

Abstract

An association between obesity and carpal tunnel syndrome is found in many epidemiological studies. Therefore, there is a need to evaluate the physiopathological links that could explain the association between these two entities. Ectopic adipose tissue is responsible for metabolic syndrome and inflammation, [...] Read more.

An association between obesity and carpal tunnel syndrome is found in many epidemiological studies. Therefore, there is a need to evaluate the physiopathological links that could explain the association between these two entities. Ectopic adipose tissue is responsible for metabolic syndrome and inflammation, and is a major risk factor for diabetes and cardiovascular diseases. Taking these elements into consideration, we conducted an extensive literature revision of the subject, considering as ectopic fat-related mechanisms the following: (a) the direct compression and the association with the metabolic syndrome of the fat deposition around the wrist, (b) the insulin resistance, dyslipidemia, inflammatory, and oxidative mechanisms related to the central deposition of the fat, (c) the impaired muscle contraction and metabolism related to myosteatosis. Each section presents the cellular pathways which are modified by the ectopic deposition of the adipose tissue and the impact in the pathogeny of the carpal tunnel syndrome. In conclusion, the experimental and clinical data support the epidemiological findings. Efforts to reduce the obesity epidemics will improve not only cardio-metabolic health but will reduce the burden of the disability-free life expectancy due to the carpal tunnel syndrome. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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12 pages, 1412 KiB

Open AccessArticle

Vasoconstrictor and Pressor Effects of Des-Aspartate-Angiotensin I in Rat

by Rosemary Wangensteen, Manuel Gómez-Guzmán, Inmaculada Banegas, Isabel Rodríguez-Gómez, Rosario Jiménez, Juan Duarte, Joaquín García-Estañ and Félix Vargas

Biomedicines 2022, 10(6), 1230; https://doi.org/10.3390/biomedicines10061230 - 25 May 2022

Viewed by 2313

Abstract

This study investigated the vasoactive effects of des-aspartate-angiotensin-I (DAA-I) in male Wistar rats on whole body vascular bed, isolated perfused kidneys, and aortic rings. Dose–response curves to DAA-I were compared with those to angiotensin II (Ang II). The Ang II-type-1 (AT1) receptor blocker, [...] Read more.

This study investigated the vasoactive effects of des-aspartate-angiotensin-I (DAA-I) in male Wistar rats on whole body vascular bed, isolated perfused kidneys, and aortic rings. Dose–response curves to DAA-I were compared with those to angiotensin II (Ang II). The Ang II-type-1 (AT1) receptor blocker, losartan, was used to evaluate the role of AT1 receptors in the responses to DAA-I. Studies were also conducted of the responsiveness in aortic rings after endothelium removal, nitric oxide synthase inhibition, or AT2 receptor blockade. DAA-I induced a dose-related systemic pressor response that was shifted to the right compared with Ang II. Losartan markedly attenuated the responsiveness to DAA-I. DAA-I showed a similar pattern in renal vasculature and aortic rings. In aortic rings, removal of endothelium and nitric oxide inhibition increased the sensitivity and maximal response to DAA-I and Ang II. AT2 receptor blockade did not significantly affect the responsiveness to DAA-I. According to these findings, DAA-I increases the systemic blood pressure and vascular tone in conductance and resistance vessels via AT1 receptor activation. This vasoconstrictor effect of DAA-I participates in the homeostatic control of arterial pressure, which can also contribute to the pathogenesis of hypertension. DAA-I may therefore be a potential therapeutic target in cardiovascular disease. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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13 pages, 965 KiB

Open AccessReview

Calcium–Permeable Channels and Endothelial Dysfunction in Acute Lung Injury

by Ying Hao, Zhuang Wang, Francis Frimpong and Xingjuan Chen

Curr. Issues Mol. Biol. 2022, 44(5), 2217-2229; https://doi.org/10.3390/cimb44050150 - 16 May 2022

Cited by 13 | Viewed by 3096

Abstract

The increased permeability of the lung microvascular endothelium is one critical initiation of acute lung injury (ALI). The disruption of vascular-endothelium integrity results in leakiness of the endothelial barrier and accumulation of protein-rich fluid in the alveoli. During ALI, increased endothelial-cell (EC) permeability [...] Read more.

The increased permeability of the lung microvascular endothelium is one critical initiation of acute lung injury (ALI). The disruption of vascular-endothelium integrity results in leakiness of the endothelial barrier and accumulation of protein-rich fluid in the alveoli. During ALI, increased endothelial-cell (EC) permeability is always companied by high frequency and amplitude of cytosolic Ca²⁺ oscillations. Mechanistically, cytosolic calcium oscillations include calcium release from internal stores and calcium entry via channels located in the cell membrane. Recently, numerous publications have shown substantial evidence that calcium-permeable channels play an important role in maintaining the integrity of the endothelium barrier function of the vessel wall in ALI. These novel endothelial signaling pathways are future targets for the treatment of lung injury. This short review focuses on the up-to-date research and provide insight into the contribution of calcium influx via ion channels to the disruption of lung microvascular endothelial-barrier function during ALI. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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8 pages, 2225 KiB

Open AccessArticle

Sostdc1 Secreted from Cutaneous Lymphatic Vessels Acts as a Paracrine Factor for Hair Follicle Growth

by Sun-Young Yoon and Michael Detmar

Curr. Issues Mol. Biol. 2022, 44(5), 2167-2174; https://doi.org/10.3390/cimb44050146 - 12 May 2022

Cited by 9 | Viewed by 3548

Abstract

In our previous study, we found that lymphatic vessels stimulate hair follicle growth through paracrine effects on dermal papilla cells. However, the paracrine factors secreted from cutaneous lymphatic vessels that can activate dermal papilla cells are still unknown. In this study, we investigated [...] Read more.

In our previous study, we found that lymphatic vessels stimulate hair follicle growth through paracrine effects on dermal papilla cells. However, the paracrine factors secreted from cutaneous lymphatic vessels that can activate dermal papilla cells are still unknown. In this study, we investigated whether lymphatic endothelial cells might secrete paracrine factors that activate dermal papilla cells in vitro. We found that Sostdc1 was more expressed in lymphatic endothelial cells compared with blood vascular endothelial cells. In addition, Sostdc1 expression levels were significantly increased during the anagen phase in the back skin of C57BL/6J mice, as compared to the telogen phase. We also observed that incubation of dermal papilla cells with 200 ng/mL Sostdc1 for 72 h induced the expression levels of Lef-1, a downstream target of Wnt signaling. Taken together, our results reveal that Sostdc1, a BMP antagonist, secreted from cutaneous lymphatic vessels, may act as a paracrine factor for hair follicle growth. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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16 pages, 2282 KiB

Open AccessReview

New Insights into Hematopoietic Stem Cell Expansion to Stimulate Repopulation of the Adult Blood System for Transplantation

by Jiangying Xuan, Yingxia Liu, Jinhui Liu, Xiaoping Zeng and Hongmei Wang

Life 2022, 12(5), 716; https://doi.org/10.3390/life12050716 - 11 May 2022

Cited by 1 | Viewed by 5872

Abstract

Successful engraftment of hematopoietic stem cells (HSCs) and progenitor cells (HSPCs) may be considered as a basis for the repopulation of the blood cells after transplantation in adults. Therefore, in vivo and ex vivo expansion of HSCs holds great promise for clinical applications. [...] Read more.

Successful engraftment of hematopoietic stem cells (HSCs) and progenitor cells (HSPCs) may be considered as a basis for the repopulation of the blood cells after transplantation in adults. Therefore, in vivo and ex vivo expansion of HSCs holds great promise for clinical applications. In this review, the mechanisms of HSC expansion will be discussed, considering the previous studies and works of literature. This is aimed to identify the signaling pathways that regulate HSC expansion and improve the application of engraftment in disease management. The following aspects will be included: (i) Stimulation of HSCs growth in vivo through gene regulation and cytokines activation; (ii) direct or indirect induction of HSC expansion by regulating signaling pathways; (iii) addition to assisting cells to help in the proliferation of HSCs; (iv) changing of living environment in the HSCs cultures via adjusting components and forms of cultures; (v) enhancement of HSC expansion by incorporating substances, such as extracellular vesicles (EVs), UM171, among others. In this review, recent new findings that provide us with new insights into HSC expansion methods have been summarized. Furthermore, these findings will also provide more possibilities for the development of some novel strategies for expanding and engrafting HSCs applied for treatments of some hematopoietic disorders. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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13 pages, 1243 KiB

Open AccessArticle

MicroRNA 320a and Membrane Antigens as Tools to Evaluate the Pathophysiology of Platelets Stored in Blood Banks

by Priscilla Cristina Moura Vieira, Jersey Heitor da Silva Maués, Letícia Martins Lamarão, Caroline Aquino Moreira-Nunes and Rommel Mário Rodríguez Burbano

Curr. Issues Mol. Biol. 2022, 44(5), 1838-1850; https://doi.org/10.3390/cimb44050126 - 22 Apr 2022

Cited by 2 | Viewed by 2016

Abstract

Our research group, through the analysis of miRNomes in platelet concentrates (PCs) stored in blood banks, identified and validated the miR-127 and miR-320a miRNAs as biomarkers of platelet storage lesions (PSLs) in PCs. In order to validate the miRNAs 127 and 320a methodologically, [...] Read more.

Our research group, through the analysis of miRNomes in platelet concentrates (PCs) stored in blood banks, identified and validated the miR-127 and miR-320a miRNAs as biomarkers of platelet storage lesions (PSLs) in PCs. In order to validate the miRNAs 127 and 320a methodologically, as PSL biomarkers in a large number of PC bags, we also evaluated important immunological markers involved in the platelet activation/aggregation process—the CD62P receptor (P-selectin), the surface glycoproteins (GP) IIb/IIIa, and the purinergic P2Y12 receptor—via flow cytometry. The miRNAs miR-127 and miR-320a were quantified by real-time quantitative PCR (RT-qPCR). To carry out this study, 500 collection tubes were used at the upper edge of the PC bags containing platelets. Each tube was divided into seven equal parts (totaling 3500 samples) for platelet analysis from 7 different storage days, where the 1st day represents the high-quality control, and the 7th day corresponds to the low-quality control of the platelets. After analyzing all parameters during storage days, it was concluded that the relative quantification of miR-320a below 0.50 and the CD62P receptor below 27.92% are reliable indicators of the absence of storage lesions in blood banks. We believe that the values found in the expression of the CD62P receptor legitimize the use of the miR-320a and miR-127 miRNAs to build a kit capable of accurately measuring whether the stored platelets are suitable for transfusion. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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12 pages, 760 KiB

Open AccessArticle

Associations of APOE Gene Variants rs429358 and rs7412 with Parameters of the Blood Lipid Profile and the Risk of Myocardial Infarction and Death in a White Population of Western Siberia

by Sergey Semaev, Elena Shakhtshneider, Liliya Shcherbakova, Dinara Ivanoshchuk, Pavel Orlov, Sophia Malyutina, Valery Gafarov, Yuliya Ragino and Mikhail Voevoda

Curr. Issues Mol. Biol. 2022, 44(4), 1713-1724; https://doi.org/10.3390/cimb44040118 - 13 Apr 2022

Cited by 7 | Viewed by 3676

Abstract

The present study aimed to analyze possible associations of rs7412 and rs429358 of the APOE gene with lipid profile parameters, the risk of myocardial infarction, and death in the mostly white population of Western Siberia (Russia). The study population was selected from a [...] Read more.

The present study aimed to analyze possible associations of rs7412 and rs429358 of the APOE gene with lipid profile parameters, the risk of myocardial infarction, and death in the mostly white population of Western Siberia (Russia). The study population was selected from a sample surveyed within the framework of the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) study (9360 subjects, age 53.8 ± 7.0 years, males/females 50/50). PCR was conducted with fluorescence detection according to the TaqMan principle on a real-time PCR machine. The frequency of a minor allele (C) of rs429358 was 0.13, and the frequency of a minor allele (T) of rs7412 was 0.09. In our study, the woman with the rare ɛ1/ɛ4 genotype had substantial aberrations in blood lipid levels. In Kaplan–Meier curves, statistically significant differences were revealed in the prognosis of survival within the subgroup of females who had a myocardial infarction (p = 0.0006): the prognosis was worse for carriers of the ɛ2/ɛ2 genotype and for ɛ4/ɛ4 carriers. Survival analysis regarding deaths from all causes showed (p = 0.0238) that female carriers of the ɛ2/ɛ4 genotype had a worse prognosis than did carriers of other genotypes. Thus, in the population of Western Siberia (Russia), we confirmed statistically significant associations between rs7412 & rs429358 genotypes and lipid profile parameters. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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12 pages, 5046 KiB

Open AccessArticle

Increased Production of Interleukin-10 and Tumor Necrosis Factor-Alpha in Stimulated Peripheral Blood Mononuclear Cells after Inhibition of S100A12

by Huang-Pin Wu, Chien-Ming Chu, Pi-Hua Liu, Shaw-Woei Leu, Shih-Wei Lin, Han-Chung Hu, Kuo-Chin Kao, Li-Fu Li and Chung-Chieh Yu

Curr. Issues Mol. Biol. 2022, 44(4), 1701-1712; https://doi.org/10.3390/cimb44040117 - 12 Apr 2022

Cited by 4 | Viewed by 3292

Abstract

Sepsis may induce immunosuppression and result in death. S100A12 can bind to the receptor for advanced glycation end-products (RAGE) and Toll-like receptor (TLR)4 following induction of various inflammatory responses. It is unclear whether S100A12 significantly influences the immune system, which may be associated [...] Read more.

Sepsis may induce immunosuppression and result in death. S100A12 can bind to the receptor for advanced glycation end-products (RAGE) and Toll-like receptor (TLR)4 following induction of various inflammatory responses. It is unclear whether S100A12 significantly influences the immune system, which may be associated with sepsis-related mortality. We measured plasma S100A12 levels and cytokine responses (mean ± standard error mean) of lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) after S100A12 inhibition in healthy controls and patients with sepsis on days one and seven. Day one plasma soluble RAGE (sRAGE) and S100A12 levels in patients with sepsis were significantly higher than those in controls (2481.3 ± 295.0 vs. 1273.0 ± 108.2 pg/mL, p < 0.001; 530.3 ± 18.2 vs. 310.1 ± 28.1 pg/mL, p < 0.001, respectively). Day seven plasma S100A12 levels in non-survivors were significantly higher than those in survivors (593.1 ± 12.7 vs. 499.3 ± 23.8 pg/mL, p = 0.002, respectively). In survivors, plasma sRAGE levels were significantly decreased after 6 days (2297.3 ± 320.3 vs. 1530.1 ± 219.1 pg/mL, p = 0.009, respectively), but not in non-survivors. Inhibiting S100A12 increased the production of tumor necrosis factor (TNF)-α and interleukin (IL)-10 in stimulated PBMCs for both controls and patients. Therefore, S100A12 plays an important role in sepsis pathogenesis. S100A12 may competitively bind to TLR4 and RAGE, resulting in decreased IL-10 and TNF-α production. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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15 pages, 3368 KiB

Open AccessArticle

Anticancer and Apoptotic Activity in Cervical Adenocarcinoma HeLa Using Crude Extract of Ganoderma applanatum

by Anley Teferra Kiddane, Min-Jae Kang, Truc Cong Ho, Adane Tilahun Getachew, Maheshkumar Prakash Patil, Byung-Soo Chun and Gun-Do Kim

Curr. Issues Mol. Biol. 2022, 44(3), 1012-1026; https://doi.org/10.3390/cimb44030067 - 22 Feb 2022

Cited by 10 | Viewed by 4282

Abstract

Cancer is currently one of the foremost health challenges and a leading cause of death worldwide. Cervical cancer is caused by cofactors, including oral contraceptive use, smoking, multiparity, and HIV infection. One of the major and considerable etiologies is the persistent infection of [...] Read more.

Cancer is currently one of the foremost health challenges and a leading cause of death worldwide. Cervical cancer is caused by cofactors, including oral contraceptive use, smoking, multiparity, and HIV infection. One of the major and considerable etiologies is the persistent infection of the oncogenic human papilloma virus. G. applanatum is a valuable medicinal mushroom that has been widely used as a folk medicine for the treatment and prevention of various diseases. In this study, we obtained crude extract from G. applanatum mushroom with a subcritical water extraction method; cell viability assay was carried out and the crude extract showed an antiproliferative effect in HeLa cells with IC₅₀ of 1.55 ± 0.01 mg/mL; however, it did not show any sign of toxicity in HaCaT. Protein expression was detected by Western blot, stability of IκBα and downregulation of NFκB, IKKα, IKKβ, p-NFκB-65(Ser 536) and p-IKKα/β(Ser 176/180), suggesting loss of survival in a dose-dependent manner. RT-qPCR revealed RNA/mRNA expression; fold changes of gene expression in Apaf-1, caspase-3, cytochrome-c, caspase-9, Bax and Bak were increased, which implies apoptosis, and NFκB was decreased in a dose-dependent manner. DNA fragmentation was seen in the treatment groups as compared to the control group using gel electrophoresis. Identification and quantification of compounds were carried out by GC–MS and HPLC, respectively; 2(5H)furanone with IC₅₀ of 1.99 ± 0.01 μg/mL could be the responsible anticancer compound. In conclusion, these findings suggest the potential use of the crude extract of G. applanatum as a natural source with anticancer activity against cervical cancer. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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17 pages, 2638 KiB

Open AccessReview

Insights into the Potential Mechanisms of JAK2V617F Somatic Mutation Contributing Distinct Phenotypes in Myeloproliferative Neoplasms

by Panhong Gou, Wenchao Zhang and Stephane Giraudier

Int. J. Mol. Sci. 2022, 23(3), 1013; https://doi.org/10.3390/ijms23031013 - 18 Jan 2022

Cited by 9 | Viewed by 7388

Abstract

Myeloproliferative neoplasms (MPN) are a group of blood cancers in which the bone marrow (BM) produces an overabundance of erythrocyte, white blood cells, or platelets. Philadelphia chromosome-negative MPN has three subtypes, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The [...] Read more.

Myeloproliferative neoplasms (MPN) are a group of blood cancers in which the bone marrow (BM) produces an overabundance of erythrocyte, white blood cells, or platelets. Philadelphia chromosome-negative MPN has three subtypes, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The over proliferation of blood cells is often associated with somatic mutations, such as JAK2, CALR, and MPL. JAK2V617F is present in 95% of PV and 50–60% of ET and PMF. Based on current molecular dynamics simulations of full JAK2 and the crystal structure of individual domains, it suggests that JAK2 maintains basal activity through self-inhibition, whereas other domains and linkers directly/indirectly enhance this self-inhibited state. Nevertheless, the JAK2V617F mutation is not the only determinant of MPN phenotype, as many normal individuals carry the JAK2V617F mutation without a disease phenotype. Here we review the major MPN phenotypes, JAK-STAT pathways, and mechanisms of development based on structural biology, while also describing the impact of other contributing factors such as gene mutation allele burden, JAK-STAT-related signaling pathways, epigenetic modifications, immune responses, and lifestyle on different MPN phenotypes. The cross-linking of these elements constitutes a complex network of interactions and generates differences in individual and cellular contexts that determine the phenotypic development of MPN. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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16 pages, 2690 KiB

Open AccessArticle

Physiological, Pathological and Pharmacological Interactions of Hydrogen Sulphide and Nitric Oxide in the Myocardium of Rats with Left Ventricular Hypertrophy

by Ashfaq Ahmad

Curr. Issues Mol. Biol. 2022, 44(1), 433-448; https://doi.org/10.3390/cimb44010030 - 16 Jan 2022

Cited by 4 | Viewed by 2866

Abstract

Left ventricular hypertrophy (LVH) is characterized by increased myocardium thickness due to increased oxidative stress and downregulation of cystathione γ lyase (CSE) endothelial nitric oxide synthase (eNOS). Upregulation of CSE by hydrogen sulphide (H₂S) and ENOS by L-arginine can arrest the [...] Read more.

Left ventricular hypertrophy (LVH) is characterized by increased myocardium thickness due to increased oxidative stress and downregulation of cystathione γ lyase (CSE) endothelial nitric oxide synthase (eNOS). Upregulation of CSE by hydrogen sulphide (H₂S) and ENOS by L-arginine can arrest the progression of LVH individually. The present study explored the combined treatment of H₂S and NO in the progression of LVH, and demonstrated that the response is due to H₂S, NO or formation of either new molecule in physiological, pathological, and pharmacological in vivo settings of LVH. Exogenous administration H₂S+NO in LVH significantly reduced (all p < 0.05) systolic blood pressure (SBP) and mean arterial pressure (MAP), LV index, heart index and oxidative stress when compared to the LVH group. There was downregulation of CSE mRNA and eNOS in the heart, and exogenous administration of H₂S+NO groups upregulated eNOS MRNA while CSE MRNA remained downregulated in the hearts of the LVH group. Similar trends were observed with concentrations of H₂S and NO in the plasma and tissue. It can be concluded that combined treatment of LVH with H₂S and NO significantly ameliorate the progression of LVH by attenuating systemic hemodynamic and physical indices, and by decreasing oxidative stress. Molecular expression data in the myocardium of LVH depicts that combined treatment upregulated eNOS/NO while it downregulated CSE/H₂S pathways in in vivo settings, and it is always eNOS/NO pathways which play a major role. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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14 pages, 1999 KiB

Open AccessArticle

Recombinant Destabilase from Hirudo medicinalis Is Able to Dissolve Human Blood Clots In Vitro

by Pavel Bobrovsky, Valentin Manuvera, Izolda Baskova, Svetlana Nemirova, Alexandr Medvedev and Vassili Lazarev

Curr. Issues Mol. Biol. 2021, 43(3), 2068-2081; https://doi.org/10.3390/cimb43030143 - 20 Nov 2021

Cited by 4 | Viewed by 13795

Abstract

Leeches are amazing animals that can be classified as conditionally poisonous animals since the salivary cocktail they produce is injected directly into the victim, and its components have strictly defined biological purposes, such as preventing blood clot formation. Thrombolytic drugs are mainly aimed [...] Read more.

Leeches are amazing animals that can be classified as conditionally poisonous animals since the salivary cocktail they produce is injected directly into the victim, and its components have strictly defined biological purposes, such as preventing blood clot formation. Thrombolytic drugs are mainly aimed at treating newly formed blood clots. Aged clots are stabilized by a large number of isopeptide bonds that prevent the action of thrombolytics. These bonds are destroyed by destabilase, an enzyme of the leech’s salivary glands. Here, we conducted a pilot study to evaluate the feasibility and effectiveness of the use of destabilase in relation to blood clots formed during real pathological processes. We evaluated the isopeptidase activity of destabilase during the formation of a stabilized fibrin clot. We showed that destabilase does not affect the internal and external coagulation cascades. We calculated the dose–response curve and tested the ability of destabilase to destroy isopeptide bonds in natural blood clots. The effect of aged and fresh clots dissolving ability after treatment with destabilase coincided with the morphological characteristics of clots during surgery. Thus, recombinant destabilase can be considered as a potential drug for the treatment of aged clots, which are difficult to treat with known thrombolytics. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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18 pages, 2060 KiB

Open AccessReview

Delivery of Nitric Oxide in the Cardiovascular System: Implications for Clinical Diagnosis and Therapy

by Tianxiang Ma, Zhexi Zhang, Yu Chen, Haoran Su, Xiaoyan Deng, Xiao Liu and Yubo Fan

Int. J. Mol. Sci. 2021, 22(22), 12166; https://doi.org/10.3390/ijms222212166 - 10 Nov 2021

Cited by 19 | Viewed by 5121

Abstract

Nitric oxide (NO) is a key molecule in cardiovascular homeostasis and its abnormal delivery is highly associated with the occurrence and development of cardiovascular disease (CVD). The assessment and manipulation of NO delivery is crucial to the diagnosis and therapy of CVD, such [...] Read more.

Nitric oxide (NO) is a key molecule in cardiovascular homeostasis and its abnormal delivery is highly associated with the occurrence and development of cardiovascular disease (CVD). The assessment and manipulation of NO delivery is crucial to the diagnosis and therapy of CVD, such as endothelial dysfunction, atherosclerotic progression, pulmonary hypertension, and cardiovascular manifestations of coronavirus (COVID-19). However, due to the low concentration and fast reaction characteristics of NO in the cardiovascular system, clinical applications centered on NO delivery are challenging. In this tutorial review, we first summarized the methods to estimate the in vivo NO delivery process, based on computational modeling and flow-mediated dilation, to assess endothelial function and vulnerability of atherosclerotic plaque. Then, emerging bioimaging technologies that have the potential to experimentally measure arterial NO concentration were discussed, including Raman spectroscopy and electrochemical sensors. In addition to diagnostic methods, therapies aimed at controlling NO delivery to regulate CVD were reviewed, including the NO release platform to treat endothelial dysfunction and atherosclerosis and inhaled NO therapy to treat pulmonary hypertension and COVID-19. Two potential methods to improve the effectiveness of existing NO therapy were also discussed, including the combination of NO release platform and computational modeling, and stem cell therapy, which currently remains at the laboratory stage but has clinical potential for the treatment of CVD. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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15 pages, 2585 KiB

Open AccessArticle

Deletion of the Gamma Subunit of ENaC in Endothelial Cells Does Not Protect against Renal Ischemia Reperfusion Injury

by Stephanie M. Mutchler, Mahpara Hasan, Donald E. Kohan, Thomas R. Kleyman and Roderick J. Tan

Int. J. Mol. Sci. 2021, 22(20), 10914; https://doi.org/10.3390/ijms222010914 - 9 Oct 2021

Cited by 4 | Viewed by 2283

Abstract

Acute kidney injury due to renal ischemia-reperfusion injury (IRI) may lead to chronic or end stage kidney disease. A greater understanding of the cellular mechanisms underlying IRI are required to develop therapeutic options aimed at limiting or reversing damage from IRI. Prior work [...] Read more.

Acute kidney injury due to renal ischemia-reperfusion injury (IRI) may lead to chronic or end stage kidney disease. A greater understanding of the cellular mechanisms underlying IRI are required to develop therapeutic options aimed at limiting or reversing damage from IRI. Prior work has shown that deletion of the α subunit of the epithelial Na+ channel (ENaC) in endothelial cells protects from IRI by increasing the availability of nitric oxide. While canonical ENaCs consist of an α, β, and γ subunit, there is evidence of non-canonical ENaC expression in endothelial cells involving the α subunit. We therefore tested whether the deletion of the γ subunit of ENaC also protects mice from IRI to differentiate between these channel configurations. Mice with endothelial-specific deletion of the γ subunit and control littermates were subjected to unilateral renal artery occlusion followed by 48 h of reperfusion. No significant difference was noted in injury between the two groups as assessed by serum creatinine and blood urea nitrogen, levels of specific kidney injury markers, and histological examination. While deletion of the γ subunit did not alter infiltration of immune cells or cytokine message, it was associated with an increase in levels of total and phosphorylated endothelial nitric oxide synthase (eNOS) in the injured kidneys. Our studies demonstrate that even though deletion of the γ subunit of ENaC may allow for greater activation of eNOS, this is not sufficient to prevent IRI, suggesting the protective effects of α subunit deletion may be due, in part, to other mechanisms. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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