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Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy
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Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 May 2024 | Viewed by 19971

Special Issue Editor

Dr. Andrea Ghiroldi

E-Mail Website
Guest Editor
Institute of Molecular and Translational Cardiology of IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy
Interests: cardiovascular diseases; biomarker discovery; biochemistry; Brugada syndrome; ischemia and reperfusion injury; sphingolipids

Special Issue Information

Dear Colleagues,

Cardiovascular diseases (CVDs) are a leading cause of death and disability worldwide. They are a group of conditions that affect the heart and blood vessels, including coronary artery disease, heart failure, and stroke. The pathogenic mechanism of CVDs is complex and multifactorial, involving a combination of genetic, environmental, and lifestyle factors.

Studying the pathogenic mechanism of CVDs is crucial for developing effective prevention and treatment strategies. Understanding the underlying causes of CVDs can lead to the identification of new therapeutic targets and the development of novel drugs. Additionally, knowledge of the pathogenic mechanism can inform the development of targeted prevention and early detection programs, which can reduce the burden of CVDs on individuals and society.

Research on the pathogenic mechanism of CVDs has made significant progress in recent years, with the identification of novel risk factors and the discovery of new genetic and molecular mechanisms. However, much remains to be understood, and ongoing research is needed to further our understanding of the underlying causes of CVDs.

This special issue will gather articles on the research advancement in CVDs in terms of pathogenic mechanism, genetic association and novel therapeutical approach.

Dr. Andrea Ghiroldi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cardiovascular diseases
  • pathogenic mechanisms
  • genetics
  • cardiomyopathy
  • myocardial infarction
  • cardiac fibrosis
  • pharmacogenomics
  • drug discovery

Published Papers (16 papers)

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Research

Jump to: Review

14 pages, 913 KiB  
Article
Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial Dysfunction
by Maxim Sinitsky, Egor Repkin, Anna Sinitskaya, Victoria Markova, Daria Shishkova and Olga Barbarash
Int. J. Mol. Sci. 2024, 25(7), 4044; https://doi.org/10.3390/ijms25074044 - 05 Apr 2024
Viewed by 534
Abstract
Mitomycin C (MMC)-induced genotoxic stress can be considered to be a novel trigger of endothelial dysfunction and atherosclerosis—a leading cause of cardiovascular morbidity and mortality worldwide. Given the increasing genotoxic load on the human organism, the decryption of the molecular pathways underlying genotoxic [...] Read more.
Mitomycin C (MMC)-induced genotoxic stress can be considered to be a novel trigger of endothelial dysfunction and atherosclerosis—a leading cause of cardiovascular morbidity and mortality worldwide. Given the increasing genotoxic load on the human organism, the decryption of the molecular pathways underlying genotoxic stress-induced endothelial dysfunction could improve our understanding of the role of genotoxic stress in atherogenesis. Here, we performed a proteomic profiling of human coronary artery endothelial cells (HCAECs) and human internal thoracic endothelial cells (HITAECs) in vitro that were exposed to MMC to identify the biochemical pathways and proteins underlying genotoxic stress-induced endothelial dysfunction. We denoted 198 and 71 unique, differentially expressed proteins (DEPs) in the MMC-treated HCAECs and HITAECs, respectively; only 4 DEPs were identified in both the HCAECs and HITAECs. In the MMC-treated HCAECs, 44.5% of the DEPs were upregulated and 55.5% of the DEPs were downregulated, while in HITAECs, these percentages were 72% and 28%, respectively. The denoted DEPs are involved in the processes of nucleotides and RNA metabolism, vesicle-mediated transport, post-translation protein modification, cell cycle control, the transport of small molecules, transcription and signal transduction. The obtained results could improve our understanding of the fundamental basis of atherogenesis and help in the justification of genotoxic stress as a risk factor for atherosclerosis. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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9 pages, 467 KiB  
Communication
Lack of Association between Serum Chitotriosidase Activity and Arterial Stiffness in Type 2 Diabetes without Cardiovascular Complications
by Luca D’Onofrio, Rocco Amendolara, Carmen Mignogna, Gaetano Leto, Lida Tartaglione, Sandro Mazzaferro, Ernesto Maddaloni and Raffaella Buzzetti
Int. J. Mol. Sci. 2023, 24(21), 15809; https://doi.org/10.3390/ijms242115809 - 31 Oct 2023
Viewed by 698
Abstract
Chitotriosidase (CHIT), a mammalian chitinase secreted by neutrophils and activated macrophages, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. The aim of this study is to evaluate [...] Read more.
Chitotriosidase (CHIT), a mammalian chitinase secreted by neutrophils and activated macrophages, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. The aim of this study is to evaluate CHIT activity as an early biomarker of arterial stiffness in people with T2D free from overt vascular complications. In this cross-sectional study, arterial stiffness as measured using standard pulse wave velocity (PWV) was evaluated in 174 people with T2D without overt vascular disease. Then, we measured CHIT serum activity with an electrochemiluminescence assay in two subgroups of participants: 35 with the highest (high-PWV) and 40 with the lowest (low-PWV) PWV values. CHIT activity was no different between the low-PVW and high-PWV groups (12.7 [9.6–17.9] vs. 11.4 [8.8–15.0] nmol/mL/h, respectively). Compared with the low-PWV group, the high-PWV participants were older (p < 0.001); had a longer duration of diabetes (p = 0.03); higher ankle–brachial index ABI (p = 0.04), systolic blood pressure (p = 0.002), diastolic blood pressure (p = 0.005), fasting blood glucose (p = 0.008), and HbA1c (p = 0.005); and lower eGFR (p = 0.03) and body mass index (BMI) (p = 0.01). No association was present with sex, duration of diabetes, age, BMI, peripheral blood pressure, laboratory parameters, and glucose-lowering medications or ongoing antihypertensive therapy. Although no association was found, this study provides novel data about the association of CHIT activity with CVD, focusing on a specific outcome (arterial stiffness) in a well-defined population of subjects with T2D without established CVD. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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19 pages, 4611 KiB  
Article
Doxorubicin-Induced Cardiomyopathy: A Preliminary Study on the Cardioprotective Benefits of 7-Hydroxyflavanone
by Nonhlakanipho F. Sangweni, Kwazi Gabuza, Ruzayda van Aarde, Lawrence Mabasa, Derick van Vuuren, Barbara Huisamen, Reenen Barry and Rabia Johnson
Int. J. Mol. Sci. 2023, 24(20), 15395; https://doi.org/10.3390/ijms242015395 - 20 Oct 2023
Viewed by 908
Abstract
The therapeutic properties of flavonoids are reported to offer cardioprotective benefits against doxorubicin (Dox)-induced cardiotoxicity (DIC). In the current study, we aimed to investigate the prophylactic properties of 7-hydroxyflavanone (7H), a flavonoid with antioxidative properties, against DIC. An in vitro model of DIC [...] Read more.
The therapeutic properties of flavonoids are reported to offer cardioprotective benefits against doxorubicin (Dox)-induced cardiotoxicity (DIC). In the current study, we aimed to investigate the prophylactic properties of 7-hydroxyflavanone (7H), a flavonoid with antioxidative properties, against DIC. An in vitro model of DIC was established by exposing H9c2 cardiomyoblasts to Dox for 6 days. Similarly, cells were also co-treated with 7H to assess its ability to mitigate DIC. The data obtained indicate that 7H, as a co-treatment, alleviates Dox-induced oxidative stress by enhancing total glutathione content (p ≤ 0.001) and superoxide dismutase activity (p ≤ 0.001) whilst decreasing ROS (p ≤ 0.001), malondialdehyde production (p ≤ 0.001) and the secretion of interleukin-6 (p ≤ 0.001). The data also showed an improvement in mitochondrial function as shown via enhanced bioenergetics, mitochondrial membrane potential, and PGC1-alpha (p ≤ 0.05) and pAMPK (p ≤ 0.001) expression. The cardioprotective potential of 7H was further highlighted by its ability attenuate Dox-induced caspase 3/7 activity (p ≤ 0.001), apoptosis (p ≤ 0.001) and necrosis (p ≤ 0.05). In conclusion, our findings demonstrated the cardioprotective benefits of 7H and thus suggests that it could be a suitable candidate cardioprotective agent against DIC. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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18 pages, 8319 KiB  
Article
miR-632 Induces DNAJB6 Inhibition Stimulating Endothelial-to-Mesenchymal Transition and Fibrosis in Marfan Syndrome Aortopathy
by Sonia Terriaca, Maria Giovanna Scioli, Calogera Pisano, Giovanni Ruvolo, Amedeo Ferlosio and Augusto Orlandi
Int. J. Mol. Sci. 2023, 24(20), 15133; https://doi.org/10.3390/ijms242015133 - 13 Oct 2023
Cited by 2 | Viewed by 933
Abstract
Marfan syndrome (MFS) is a connective tissue disorder caused by FBN1 gene mutations leading to TGF-β signaling hyperactivation, vascular wall weakness, and thoracic aortic aneurysms (TAAs). The pathogenetic mechanisms are not completely understood and patients undergo early vascular surgery to prevent TAA ruptures. [...] Read more.
Marfan syndrome (MFS) is a connective tissue disorder caused by FBN1 gene mutations leading to TGF-β signaling hyperactivation, vascular wall weakness, and thoracic aortic aneurysms (TAAs). The pathogenetic mechanisms are not completely understood and patients undergo early vascular surgery to prevent TAA ruptures. We previously reported miR-632 upregulation in MFS TAA tissues compared with non-genetic TAA tissues. DNAJB6 is a gene target of miR-632 in cancer and plays a critical role in blocking epithelial-to-mesenchymal transition by inhibiting the Wnt/β catenin pathway. TGF-β signaling also activates Wnt/β catenin signaling and induces endothelial-to-mesenchymal transition (End-Mt) and fibrosis. We documented that miR-632 upregulation correlated with DNAJB6 expression in both the endothelium and the tunica media of MFS TAA (p < 0.01). Wnt/β catenin signaling, End-Mt, and fibrosis markers were also upregulated in MFS TAA tissues (p < 0.05, p < 0.01 and p < 0.001). Moreover, miR-632 overexpression inhibited DNAJB6, inducing Wnt/β catenin signaling, as well as End-Mt and fibrosis exacerbation (p < 0.05 and p < 0.01). TGF-β1 treatment also determined miR-632 upregulation (p < 0.01 and p < 0.001), with the consequent activation of the aforementioned processes. Our study provides new insights about the pathogenetic mechanisms in MFS aortopathy. Moreover, the high disease specificity of miR-632 and DNAJB6 suggests new potential prognostic factors and/or therapeutic targets in the progression of MFS aortopathy. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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9 pages, 2196 KiB  
Communication
Systemic Effects of Homoarginine Supplementation on Arginine Metabolizing Enzymes in Rats with Heart Failure with Preserved Ejection Fraction
by Petra Büttner, Sarah Werner, Julia Böttner, Susann Ossmann, Edzard Schwedhelm and Holger Thiele
Int. J. Mol. Sci. 2023, 24(19), 14782; https://doi.org/10.3390/ijms241914782 - 30 Sep 2023
Viewed by 728
Abstract
A restoration of low homoarginine (hArg) levels in obese ZSF1 rats (O-ZSF1) before (S1-ZSF1) and after (S2-ZSF1) the manifestation of heart failure with preserved ejection fraction (HFpEF) did not affect the worsening of cardiac HFpEF characteristics. Here, potential regulation of key enzymes of [...] Read more.
A restoration of low homoarginine (hArg) levels in obese ZSF1 rats (O-ZSF1) before (S1-ZSF1) and after (S2-ZSF1) the manifestation of heart failure with preserved ejection fraction (HFpEF) did not affect the worsening of cardiac HFpEF characteristics. Here, potential regulation of key enzymes of arginine metabolism in other organs was analyzed. Arginase 2 (ARG2) was reduced >35% in the kidney and small intestine of hArg-supplemented rats compared to O-ZSF1. Glycine amidinotransferase (GATM) was 29% upregulated in the kidneys of S1-ZSF1. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) levels were reduced >50% in the livers of O-ZSF1 but restored in S2-ZSF1 compared to healthy rats (L-ZSF1). In the skeletal muscle, iNOS was lower in O-ZSF1 and further decreased in S1-ZSF1 and S2-ZSF1 compared to L-ZSF1. iNOS levels were lower in the liver of the S2-ZSF1 group but higher in the kidneys of S1-ZSF1 compared to L-ZSF1. Supplementation with hArg in an in vivo HFpEF model resulted in the inhibition of renal ARG2 and an increase in GATM expression. This supplementation might contribute to the stabilization of intestinal iNOS and ARG2 imbalances, thereby enhancing barrier function. Additionally, it may offer protective effects in skeletal muscle by downregulating iNOS. In the conceptualization of hArg supplementation studies, the current disease progression stage as well as organ-specific enzyme regulation should be considered. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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16 pages, 6891 KiB  
Article
mTOR Inhibitors Modulate the Physical Properties of 3D Spheroids Derived from H9c2 Cells
by Megumi Watanabe, Toshiyuki Yano, Tatsuya Sato, Araya Umetsu, Megumi Higashide, Masato Furuhashi and Hiroshi Ohguro
Int. J. Mol. Sci. 2023, 24(14), 11459; https://doi.org/10.3390/ijms241411459 - 14 Jul 2023
Cited by 2 | Viewed by 1225
Abstract
To establish an appropriate in vitro model for the local environment of cardiomyocytes, three-dimensional (3D) spheroids derived from H9c2 cardiomyoblasts were prepared, and their morphological, biophysical phase contrast and biochemical characteristics were evaluated. The 3D H9c2 spheroids were successfully obtained, the sizes of [...] Read more.
To establish an appropriate in vitro model for the local environment of cardiomyocytes, three-dimensional (3D) spheroids derived from H9c2 cardiomyoblasts were prepared, and their morphological, biophysical phase contrast and biochemical characteristics were evaluated. The 3D H9c2 spheroids were successfully obtained, the sizes of the spheroids decreased, and they became stiffer during 3–4 days. In contrast to the cell multiplication that occurs in conventional 2D planar cell cultures, the 3D H9c2 spheroids developed into a more mature form without any cell multiplication being detected. qPCR analyses of the 3D H9c2 spheroids indicated that the production of collagen4 (COL4) and fibronectin (FN), connexin43 (CX43), β-catenin, N-cadherin, STAT3, and HIF1 molecules had increased and that the production of COL6 and α-smooth muscle actin (α-SMA) molecules had decreased as compared to 2D cultured cells. In addition, treatment with rapamycin (Rapa), an mTOR complex (mTORC) 1 inhibitor, and Torin 1, an mTORC1/2 inhibitor, resulted in significantly decreased cell densities of the 2D cultured H9c2 cells, but the size and stiffness of the H9c2 cells within the 3D spheroids were reduced with the gene expressions of several of the above several factors being reduced. The metabolic responses to mTOR modulators were also different between the 2D and 3D cultures. These results suggest that as unique aspects of the local environments of the 3D spheroids, the spontaneous expression of GJ-related molecules and hypoxia within the core may be associated with their maturation, suggesting that this may become a useful in vitro model that replicates the local environment of cardiomyocytes. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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18 pages, 5569 KiB  
Article
Lamin A/C Ablation Restricted to Vascular Smooth Muscle Cells, Cardiomyocytes, and Cardiac Fibroblasts Causes Cardiac and Vascular Dysfunction
by Alberto Del Monte-Monge, Íñigo Ruiz-Polo de Lara, Pilar Gonzalo, Carla Espinós-Estévez, María González-Amor, Miguel de la Fuente-Pérez, María J. Andrés-Manzano, Víctor Fanjul, Juan R. Gimeno, Roberto Barriales-Villa, Beatriz Dorado and Vicente Andrés
Int. J. Mol. Sci. 2023, 24(13), 11172; https://doi.org/10.3390/ijms241311172 - 06 Jul 2023
Viewed by 1641
Abstract
Mutations in the LMNA gene (encoding lamin A/C proteins) cause several human cardiac diseases, including dilated cardiomyopathies (LMNA-DCM). The main clinical risks in LMNA-DCM patients are sudden cardiac death and progressive left ventricular ejection fraction deterioration, and therefore most human [...] Read more.
Mutations in the LMNA gene (encoding lamin A/C proteins) cause several human cardiac diseases, including dilated cardiomyopathies (LMNA-DCM). The main clinical risks in LMNA-DCM patients are sudden cardiac death and progressive left ventricular ejection fraction deterioration, and therefore most human and animal studies have sought to define the mechanisms through which LMNA mutations provoke cardiac alterations, with a particular focus on cardiomyocytes. To investigate if LMNA mutations also cause vascular alterations that might contribute to the etiopathogenesis of LMNA-DCM, we generated and characterized Lmnaflox/floxSM22αCre mice, which constitutively lack lamin A/C in vascular smooth muscle cells (VSMCs), cardiac fibroblasts, and cardiomyocytes. Like mice with whole body or cardiomyocyte-specific lamin A/C ablation, Lmnaflox/floxSM22αCre mice recapitulated the main hallmarks of human LMNA-DCM, including ventricular systolic dysfunction, cardiac conduction defects, cardiac fibrosis, and premature death. These alterations were associated with elevated expression of total and phosphorylated (active) Smad3 and cleaved (active) caspase 3 in the heart. Lmnaflox/floxSM22αCre mice also exhibited perivascular fibrosis in the coronary arteries and a switch of aortic VSMCs from the ‘contractile’ to the ‘synthetic’ phenotype. Ex vivo wire myography in isolated aortic rings revealed impaired maximum contraction capacity and an altered response to vasoconstrictor and vasodilator agents in Lmnaflox/floxSM22αCre mice. To our knowledge, our results provide the first evidence of phenotypic alterations in VSMCs that might contribute significantly to the pathophysiology of some forms of LMNA-DCM. Future work addressing the mechanisms underlying vascular defects in LMNA-DCM may open new therapeutic avenues for these diseases. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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23 pages, 8664 KiB  
Article
Myokine Musclin Is Critical for Exercise-Induced Cardiac Conditioning
by Matthew P. Harris, Shemin Zeng, Zhiyong Zhu, Vitor A. Lira, Liping Yu, Denice M. Hodgson-Zingman and Leonid V. Zingman
Int. J. Mol. Sci. 2023, 24(7), 6525; https://doi.org/10.3390/ijms24076525 - 30 Mar 2023
Cited by 2 | Viewed by 2275
Abstract
This study investigates the role and mechanisms by which the myokine musclin promotes exercise-induced cardiac conditioning. Exercise is one of the most powerful triggers of cardiac conditioning with proven benefits for healthy and diseased hearts. There is an emerging understanding that muscles produce [...] Read more.
This study investigates the role and mechanisms by which the myokine musclin promotes exercise-induced cardiac conditioning. Exercise is one of the most powerful triggers of cardiac conditioning with proven benefits for healthy and diseased hearts. There is an emerging understanding that muscles produce and secrete myokines, which mediate local and systemic “crosstalk” to promote exercise tolerance and overall health, including cardiac conditioning. The myokine musclin, highly conserved across animal species, has been shown to be upregulated in response to physical activity. However, musclin effects on exercise-induced cardiac conditioning are not established. Following completion of a treadmill exercise protocol, wild type (WT) mice and mice with disruption of the musclin-encoding gene, Ostn, had their hearts extracted and exposed to an ex vivo ischemia-reperfusion protocol or biochemical studies. Disruption of musclin signaling abolished the ability of exercise to mitigate cardiac ischemic injury. This impaired cardioprotection was associated with reduced mitochondrial content and function linked to blunted cyclic guanosine monophosphate (cGMP) signaling. Genetic deletion of musclin reduced the nuclear abundance of protein kinase G (PKGI) and cyclic adenosine monophosphate (cAMP) response element binding (CREB), resulting in suppression of the master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), and its downstream targets in response to physical activity. Synthetic musclin peptide pharmacokinetic parameters were defined and used to calculate the infusion rate necessary to maintain its plasma level comparable to that observed after exercise. This infusion was found to reproduce the cardioprotective benefits of exercise in sedentary WT and Ostn-KO mice. Musclin is essential for exercise-induced cardiac protection. Boosting musclin signaling might serve as a novel therapeutic strategy for cardioprotection. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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Review

Jump to: Research

17 pages, 1081 KiB  
Review
The Role of Inflammasome in Abdominal Aortic Aneurysm and Its Potential Drugs
by Suyu Pi, Sizheng Xiong, Yan Yuan and Hongping Deng
Int. J. Mol. Sci. 2024, 25(9), 5001; https://doi.org/10.3390/ijms25095001 - 03 May 2024
Viewed by 196
Abstract
Abdominal aortic aneurysm (AAA) has been recognized as a serious chronic inflammatory degenerative aortic disease in recent years. At present, there is no other effective intervention except surgical treatment for AAA. With the aging of the human population, its incidence is increasing year [...] Read more.
Abdominal aortic aneurysm (AAA) has been recognized as a serious chronic inflammatory degenerative aortic disease in recent years. At present, there is no other effective intervention except surgical treatment for AAA. With the aging of the human population, its incidence is increasing year by year, posing a serious threat to human health. Modern studies suggest that vascular chronic inflammatory response is the core process in AAA occurrence and development. Inflammasome, a multiprotein complex located in the cytoplasm, mediates the expression of various inflammatory cytokines like interleukin (IL)-1β and IL-18, and thus plays a pivotal role in inflammation regulation. Therefore, inflammasome may exert a crucial influence on the progression of AAA. This article reviews some mechanism studies to investigate the role of inflammasome in AAA and then summarizes several potential drugs targeting inflammasome for the treatment of AAA, aiming to provide new ideas for the clinical prevention and treatment of AAA beyond surgical methods. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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25 pages, 2566 KiB  
Review
Use of Statins in Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives
by Artem Ovchinnikov, Alexandra Potekhina, Tatiana Arefieva, Anastasiia Filatova, Fail Ageev and Evgeny Belyavskiy
Int. J. Mol. Sci. 2024, 25(9), 4958; https://doi.org/10.3390/ijms25094958 - 01 May 2024
Viewed by 396
Abstract
Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure (HF) with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and [...] Read more.
Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure (HF) with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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25 pages, 3220 KiB  
Review
Photodynamic Therapy for Atherosclerosis
by Wiktoria Mytych, Dorota Bartusik-Aebisher, Aleksandra Łoś, Klaudia Dynarowicz, Angelika Myśliwiec and David Aebisher
Int. J. Mol. Sci. 2024, 25(4), 1958; https://doi.org/10.3390/ijms25041958 - 06 Feb 2024
Cited by 1 | Viewed by 1277
Abstract
Atherosclerosis, which currently contributes to 31% of deaths globally, is of critical cardiovascular concern. Current diagnostic tools and biomarkers are limited, emphasizing the need for early detection. Lifestyle modifications and medications form the basis of treatment, and emerging therapies such as photodynamic therapy [...] Read more.
Atherosclerosis, which currently contributes to 31% of deaths globally, is of critical cardiovascular concern. Current diagnostic tools and biomarkers are limited, emphasizing the need for early detection. Lifestyle modifications and medications form the basis of treatment, and emerging therapies such as photodynamic therapy are being developed. Photodynamic therapy involves a photosensitizer selectively targeting components of atherosclerotic plaques. When activated by specific light wavelengths, it induces localized oxidative stress aiming to stabilize plaques and reduce inflammation. The key advantage lies in its selective targeting, sparing healthy tissues. While preclinical studies are encouraging, ongoing research and clinical trials are crucial for optimizing protocols and ensuring long-term safety and efficacy. The potential combination with other therapies makes photodynamic therapy a versatile and promising avenue for addressing atherosclerosis and associated cardiovascular disease. The investigations underscore the possibility of utilizing photodynamic therapy as a valuable treatment choice for atherosclerosis. As advancements in research continue, photodynamic therapy might become more seamlessly incorporated into clinical approaches for managing atherosclerosis, providing a blend of efficacy and limited invasiveness. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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29 pages, 786 KiB  
Review
Current Medical Therapy and Revascularization in Peripheral Artery Disease of the Lower Limbs: Impacts on Subclinical Chronic Inflammation
by Andrea Leonardo Cecchini, Federico Biscetti, Matteo Manzato, Lorenzo Lo Sasso, Maria Margherita Rando, Maria Anna Nicolazzi, Enrica Rossini, Luis H. Eraso, Paul J. Dimuzio, Massimo Massetti, Antonio Gasbarrini and Andrea Flex
Int. J. Mol. Sci. 2023, 24(22), 16099; https://doi.org/10.3390/ijms242216099 - 08 Nov 2023
Cited by 1 | Viewed by 1793
Abstract
Peripheral artery disease (PAD), coronary artery disease (CAD), and cerebrovascular disease (CeVD) are characterized by atherosclerosis and inflammation as their underlying mechanisms. This paper aims to conduct a literature review on pharmacotherapy for PAD, specifically focusing on how different drug classes target pro-inflammatory [...] Read more.
Peripheral artery disease (PAD), coronary artery disease (CAD), and cerebrovascular disease (CeVD) are characterized by atherosclerosis and inflammation as their underlying mechanisms. This paper aims to conduct a literature review on pharmacotherapy for PAD, specifically focusing on how different drug classes target pro-inflammatory pathways. The goal is to enhance the choice of therapeutic plans by considering their impact on the chronic subclinical inflammation that is associated with PAD development and progression. We conducted a comprehensive review of currently published original articles, narratives, systematic reviews, and meta-analyses. The aim was to explore the relationship between PAD and inflammation and evaluate the influence of current pharmacological and nonpharmacological interventions on the underlying chronic subclinical inflammation. Our findings indicate that the existing treatments have added anti-inflammatory properties that can potentially delay or prevent PAD progression and improve outcomes, independent of their effects on traditional risk factors. Although inflammation-targeted therapy in PAD shows promising potential, its benefits have not been definitively proven yet. However, it is crucial not to overlook the pleiotropic properties of the currently available treatments, as they may provide valuable insights for therapeutic strategies. Further studies focusing on the anti-inflammatory and immunomodulatory effects of these treatments could enhance our understanding of the mechanisms contributing to the residual risk in PAD and pave the way for the development of novel therapies. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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14 pages, 972 KiB  
Review
Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Perspective from Fibroblasts
by Maja Schlittler, Peter P. Pramstaller, Alessandra Rossini and Marzia De Bortoli
Int. J. Mol. Sci. 2023, 24(19), 14845; https://doi.org/10.3390/ijms241914845 - 02 Oct 2023
Cited by 4 | Viewed by 1720
Abstract
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and the leading cause of sudden cardiac death in young people. Mutations in genes that encode structural proteins of the cardiac sarcomere are the more frequent genetic cause of HCM. The disease is [...] Read more.
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and the leading cause of sudden cardiac death in young people. Mutations in genes that encode structural proteins of the cardiac sarcomere are the more frequent genetic cause of HCM. The disease is characterized by cardiomyocyte hypertrophy and myocardial fibrosis, which is defined as the excessive deposition of extracellular matrix proteins, mainly collagen I and III, in the myocardium. The development of fibrotic tissue in the heart adversely affects cardiac function. In this review, we discuss the latest evidence on how cardiac fibrosis is promoted, the role of cardiac fibroblasts, their interaction with cardiomyocytes, and their activation via the TGF-β pathway, the primary intracellular signalling pathway regulating extracellular matrix turnover. Finally, we summarize new findings on profibrotic genes as well as genetic and non-genetic factors involved in the pathophysiology of HCM. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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17 pages, 2341 KiB  
Review
Electrical and Structural Insights into Right Ventricular Outflow Tract Arrhythmogenesis
by Yen-Yu Lu, Yao-Chang Chen, Yung-Kuo Lin, Shih-Ann Chen and Yi-Jen Chen
Int. J. Mol. Sci. 2023, 24(14), 11795; https://doi.org/10.3390/ijms241411795 - 22 Jul 2023
Cited by 3 | Viewed by 1387
Abstract
The right ventricular outflow tract (RVOT) is the major origin of ventricular arrhythmias, including premature ventricular contractions, idiopathic ventricular arrhythmias, Brugada syndrome, torsade de pointes, long QT syndrome, and arrhythmogenic right ventricular cardiomyopathy. The RVOT has distinct developmental origins and cellular characteristics and [...] Read more.
The right ventricular outflow tract (RVOT) is the major origin of ventricular arrhythmias, including premature ventricular contractions, idiopathic ventricular arrhythmias, Brugada syndrome, torsade de pointes, long QT syndrome, and arrhythmogenic right ventricular cardiomyopathy. The RVOT has distinct developmental origins and cellular characteristics and a complex myocardial architecture with high shear wall stress, which may lead to its high vulnerability to arrhythmogenesis. RVOT myocytes are vulnerable to intracellular sodium and calcium overload due to calcium handling protein modulation, enhanced CaMKII activity, ryanodine receptor phosphorylation, and a higher cAMP level activated by predisposing factors or pathological conditions. A reduction in Cx43 and Scn5a expression may lead to electrical uncoupling in RVOT. The purpose of this review is to update the current understanding of the cellular and molecular mechanisms of RVOT arrhythmogenesis. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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16 pages, 2252 KiB  
Review
The Role of Galectin-3 in Predicting Congenital Heart Disease Outcome: A Review of the Literature
by Amalia Făgărășan, Maria Săsăran, Liliana Gozar, Andrei Crauciuc and Claudia Bănescu 
Int. J. Mol. Sci. 2023, 24(13), 10511; https://doi.org/10.3390/ijms241310511 - 22 Jun 2023
Cited by 1 | Viewed by 1335
Abstract
Galectin-3 (Gal-3) is a novel pro-fibrotic biomarker that can predict both right and left cardiac dysfunction caused by various cardiovascular conditions. Its expression seems to be progressively altered with evolving cardiac remodeling processes, even before the onset of heart failure. Hence, Gal-3 has [...] Read more.
Galectin-3 (Gal-3) is a novel pro-fibrotic biomarker that can predict both right and left cardiac dysfunction caused by various cardiovascular conditions. Its expression seems to be progressively altered with evolving cardiac remodeling processes, even before the onset of heart failure. Hence, Gal-3 has been found to be an individual predictor of acute and chronic heart failure or to serve as part of an integrated biomarker panel that can foresee adverse cardiac outcomes. In congenital heart disease (CHD), Gal-3 correlates with cardiac mortality and complications in both children and adults and is proposed as a therapeutic target in order to reverse the activation of pro-fibrosis pathways that lead to heart failure. Positive associations between serum Gal-3 levels, post-operatory hospitalization rates, complications and ventricular dysfunction have also been reported within studies conducted on patients with CHD who underwent corrective surgery. Thus, this review tried to address the potential utility of Gal-3 in patients with CHD and particularly in those who undergo corrective surgery. The heterogeneity of the literature data and the lack of validation of the results obtained by the current studies on larger cohorts cannot be neglected, though. Further longitudinal research is required to establish how Gal-3 can relate to long-term outcomes in pediatric CHD. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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16 pages, 966 KiB  
Review
Target and Cell Therapy for Atherosclerosis and CVD
by Yuliya V. Markina, Tatiana V. Kirichenko, Taisiya V. Tolstik, Anastasia I. Bogatyreva, Ulyana S. Zotova, Vadim R. Cherednichenko, Anton Yu. Postnov and Alexander M. Markin
Int. J. Mol. Sci. 2023, 24(12), 10308; https://doi.org/10.3390/ijms241210308 - 18 Jun 2023
Cited by 3 | Viewed by 1717
Abstract
Cardiovascular diseases (CVD) and, in particular, atherosclerosis, remain the main cause of death in the world today. Unfortunately, in most cases, CVD therapy begins after the onset of clinical symptoms and is aimed at eliminating them. In this regard, early pathogenetic therapy for [...] Read more.
Cardiovascular diseases (CVD) and, in particular, atherosclerosis, remain the main cause of death in the world today. Unfortunately, in most cases, CVD therapy begins after the onset of clinical symptoms and is aimed at eliminating them. In this regard, early pathogenetic therapy for CVD remains an urgent problem in modern science and healthcare. Cell therapy, aimed at eliminating tissue damage underlying the pathogenesis of some pathologies, including CVD, by replacing it with various cells, is of the greatest interest. Currently, cell therapy is the most actively developed and potentially the most effective treatment strategy for CVD associated with atherosclerosis. However, this type of therapy has some limitations. In this review, we have tried to summarize the main targets of cell therapy for CVD and atherosclerosis in particular based on the analysis using the PubMed and Scopus databases up to May 2023. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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