Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0

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: closed (20 December 2022) | Viewed by 42162

Special Issue Editors

Dr. Ida Daniela Perrotta

E-Mail Website
Guest Editor
Department of Biology, Ecology and Earth Sciences, Centre for Microscopy and Microanalysis (CM2), University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy
Interests: atherosclerosis; vascular smooth muscle cell; inflammation; endothelium; cell senescence; apoptosis; lipid metabolism; oxidative stress; nitric oxide; exosomes; vascular calcification; cytokines; growth factors
Special Issues, Collections and Topics in MDPI journals
Dr. Valeria Zuccalá

E-Mail Website
Co-Guest Editor
Pathology Unit, “Pugliese-Ciaccio” Hospital, 88100 Catanzaro, Italy
Interests: cardiovascular pathology; atherosclerosis; human pathology; cancer; molecular carcinogenesis

Special Issue Information

Dear Colleagues,

Although studies on the molecular biology of atherogenesis have become the focus of modern atherosclerosis research, the multifactorial pathogenesis of the disease has not been fully elucidated to date. Atherosclerosis is a fibroproliferative disease that proceeds through a series of pathological events involving the inflammatory and immune systems as well as the different types of cells and matrix proteins of the vascular wall. The disease is accompanied by the subendothelial accumulation of lipids and fibrous connective tissue, the phenotypic modulation of SMCs, and the migration of a group of cells, notably monocytes and T cells, through the vascular endothelium in response to inflammation. Along with the traditional cardiovascular risk factors, many other molecular determinants have a role in the appearance, progression, and complication of the disease. Inflammatory cytokines, growth factors, markers of oxidative stress, cell death signals, and mediators of vascular tone all participate in the inflammatory response of atherosclerosis via multiple intricate pathways. Also, arterial wall calcification is considered a direct marker of atherosclerotic disease, yet its underlying molecular mechanisms remain to be elucidated. Other important contributors to atherosclerosis are the exosomes and their miRNAs whose role and interactions with the microenvironment of the plaque can be exploited therapeutically.

This Special Issue on “Atherosclerosis: From Molecular Biology to Therapeutic Perspectives 3.0” welcomes original research articles and reviews in the field, with a focus on (but not limited to) the molecular mechanisms mediating vascular inflammation, endothelial dysfunction, SMC biology, immune-metabolic interactions, apoptosis, cell-to-cell communication, lipid metabolism, and vascular cell senescence.

Dr. Ida Daniela Perrotta
Dr. Valeria Zuccalá
Guest Editors

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

  • atherosclerosis
  • vascular smooth muscle cell
  • inflammation
  • endothelium
  • cell senescence
  • apoptosis
  • lipid metabolism
  • oxidative stress
  • nitric oxide
  • exosomes
  • vascular calcification
  • cytokines
  • growth factors

Published Papers (17 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

4 pages, 195 KiB  
Editorial
Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0
by Ida Perrotta
Int. J. Mol. Sci. 2023, 24(8), 6897; https://doi.org/10.3390/ijms24086897 - 7 Apr 2023
Cited by 1 | Viewed by 955
Abstract
Atherosclerosis is a multifactorial chronic disease triggered and sustained by different risk factors such as dyslipidemia, hypertension, diabetes mellitus (DM), smoke, elevated homocysteine, and hormones [...] Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)

Research

Jump to: Editorial, Review

14 pages, 2912 KiB  
Article
Porphyromonas gingivalis Lipopolysaccharides Promote Proliferation and Migration of Human Vascular Smooth Muscle Cells through the MAPK/TLR4 Pathway
by Megumi Miyabe, Nobuhisa Nakamura, Tomokazu Saiki, Satoru Miyabe, Mizuho Ito, Sachiko Sasajima, Tomomi Minato, Tatsuaki Matsubara and Keiko Naruse
Int. J. Mol. Sci. 2023, 24(1), 125; https://doi.org/10.3390/ijms24010125 - 21 Dec 2022
Cited by 4 | Viewed by 1656
Abstract
Atherosclerosis is a major cause of mortality worldwide. The initial change in atherosclerosis is intimal thickening due to muscle cell proliferation and migration. A correlation has been observed between periodontal disease and atherosclerosis. Here, we investigated the proliferation and migration of human aortic [...] Read more.
Atherosclerosis is a major cause of mortality worldwide. The initial change in atherosclerosis is intimal thickening due to muscle cell proliferation and migration. A correlation has been observed between periodontal disease and atherosclerosis. Here, we investigated the proliferation and migration of human aortic smooth muscle cells (HASMCs) using Porphyromonas gingivalis-derived LPS (Pg-LPS). To elucidate intracellular signaling, toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) of HASMCs were knocked down, and the role of these molecules in Pg-LPS-stimulated proliferation and migration was examined. The role of mitogen-activated protein kinase (MAPK) in HASMC proliferation and migration was further elucidated by MAPK inhibition. Pg-LPS stimulation increased the proliferation and migration of HASMCs and activated the TLR4/MyD88 pathway. TLR4 knockdown inhibited Pg-LPS stimulated HASMCs proliferation and migration. Pg-LPS stimulation led to the phosphorylation of P38 MAPK, JNK, and ERK, and MyD88 knockdown inhibited the phosphorylation of P38 MAPK and JNK but not ERK. P38 MAPK and SAPK/JNK inhibition did not suppress the proliferation of HASMCs upon Pg-LPS stimulation, but ERK inhibition significantly inhibited proliferation. SAPK/JNK and ERK inhibition suppressed Pg-LPS-stimulated migration of HASMCs. In conclusion, our findings suggest that Pg-LPS may promote atherosclerosis via the activation of MAPK through TLR4. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

13 pages, 1432 KiB  
Article
Gαq Is the Specific Mediator of PAR-1 Transactivation of Kinase Receptors in Vascular Smooth Muscle Cells
by Danielle Kamato, Mai Gabr, Hirushi Kumarapperuma, Zheng J. Chia, Wenhua Zheng, Suowen Xu, Narin Osman and Peter J. Little
Int. J. Mol. Sci. 2022, 23(22), 14425; https://doi.org/10.3390/ijms232214425 - 20 Nov 2022
Cited by 1 | Viewed by 1711
Abstract
Aims: G protein-coupled receptor (GPCR) transactivation of kinase receptors greatly expands the actions attributable to GPCRs. Thrombin, via its cognate GPCR, protease-activated receptor (PAR)-1, transactivates tyrosine and serine/threonine kinase receptors, specifically the epidermal growth factor receptor and transforming growth factor-β receptor, respectively. PAR-1 [...] Read more.
Aims: G protein-coupled receptor (GPCR) transactivation of kinase receptors greatly expands the actions attributable to GPCRs. Thrombin, via its cognate GPCR, protease-activated receptor (PAR)-1, transactivates tyrosine and serine/threonine kinase receptors, specifically the epidermal growth factor receptor and transforming growth factor-β receptor, respectively. PAR-1 transactivation-dependent signalling leads to the modification of lipid-binding proteoglycans involved in the retention of lipids and the development of atherosclerosis. The mechanisms of GPCR transactivation of kinase receptors are distinct. We aimed to investigate the role of proximal G proteins in transactivation-dependent signalling. Main Methods: Using pharmacological and molecular approaches, we studied the role of the G⍺ subunits, G⍺q and G⍺11, in the context of PAR-1 transactivation-dependent signalling leading to proteoglycan modifications. Key Findings: Pan G⍺q subunit inhibitor UBO-QIC/FR900359 inhibited PAR-1 transactivation of kinase receptors and proteoglycans modification. The G⍺q/11 inhibitor YM254890 did not affect PAR-1 transactivation pathways. Molecular approaches revealed that of the two highly homogenous G⍺q members, G⍺q and G⍺11, only the G⍺q was involved in regulating PAR-1 mediated proteoglycan modification. Although G⍺q and G⍺11 share approximately 90% homology at the protein level, we show that the two isoforms exhibit different functional roles. Significance: Our findings may be extrapolated to other GPCRs involved in vascular pathology and highlight the need for novel pharmacological tools to assess the role of G proteins in GPCR signalling to expand the preeminent position of GPCRs in human therapeutics. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

13 pages, 4254 KiB  
Article
Development of a Method for Producing oxLDL: Characterization of Their Effects on HPV-Positive Head and Neck Cancer Cells
by Alessandro Scalia, Nadège Kindt, Anne Trelcat, Amandine Nachtergael, Pierre Duez, Fabrice Journé and Stéphane Carlier
Int. J. Mol. Sci. 2022, 23(20), 12552; https://doi.org/10.3390/ijms232012552 - 19 Oct 2022
Cited by 4 | Viewed by 1698
Abstract
Cardiovascular diseases (CVD) and cancers are the two main causes of death worldwide. The initiation and progression of atherosclerosis is, in large part, caused by oxidized low-density lipoproteins (oxLDL); interestingly, oxLDL may also play a role in cancer cell metabolism and migration. As [...] Read more.
Cardiovascular diseases (CVD) and cancers are the two main causes of death worldwide. The initiation and progression of atherosclerosis is, in large part, caused by oxidized low-density lipoproteins (oxLDL); interestingly, oxLDL may also play a role in cancer cell metabolism and migration. As oxLDL are generally obtained by tedious ultracentrifugation procedures, “home-made” oxLDL were obtained by (i) applying a purification kit to isolate LDL and VLDL from human plasma; (ii) isolating LDL from VLDL by gel permeation chromatography (GPC); and (iii) oxidating LDL through CuSO4 incubation. On three HPV-positive head and neck cancer cells (HNCC) (93VU-147T, UM-SCC47, and UPCI-SCC154), cell migration was assessed using Boyden chambers, the Wnt/ß-catenin pathway was analyzed by Western Blotting, and the expression of two oxLDL receptors, LOX-1 and CD36, in response to oxLDL exposure, was analysed by immunofluorescence. Our data indicate: (a) a non-significant difference between reference and “home-made” oxLDL; (b) a decreased migration, parallel to an inhibition of the ß-catenin pathway; and (c) an increase of CD36 and LOX-1 expression in all HNCC. In conclusion, we successfully produced oxLDL. Our results demonstrate a decrease in HNCC migration after oxLDL exposure, and an increased expression of LOX-1 and CD36 associated with lipid uptake. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

20 pages, 7818 KiB  
Article
Excessive Adventitial and Perivascular Vascularisation Correlates with Vascular Inflammation and Intimal Hyperplasia
by Leo Bogdanov, Daria Shishkova, Rinat Mukhamadiyarov, Elena Velikanova, Anna Tsepokina, Alexander Terekhov, Vladislav Koshelev, Anastasia Kanonykina, Amin Shabaev, Alexey Frolov, Nikita Zagorodnikov and Anton Kutikhin
Int. J. Mol. Sci. 2022, 23(20), 12156; https://doi.org/10.3390/ijms232012156 - 12 Oct 2022
Cited by 10 | Viewed by 1617
Abstract
Albeit multiple studies demonstrated that vasa vasorum (VV) have a crucial importance in vascular pathology, the informative markers and metrics of vascular inflammation defining the development of intimal hyperplasia (IH) have been vaguely studied. Here, we employed two rat models (balloon injury of [...] Read more.
Albeit multiple studies demonstrated that vasa vasorum (VV) have a crucial importance in vascular pathology, the informative markers and metrics of vascular inflammation defining the development of intimal hyperplasia (IH) have been vaguely studied. Here, we employed two rat models (balloon injury of the abdominal aorta and the same intervention optionally complemented with intravenous injections of calciprotein particles) and a clinical scenario (arterial and venous conduits for coronary artery bypass graft (CABG) surgery) to investigate the pathophysiological interconnections among VV, myeloperoxidase-positive (MPO+) clusters, and IH. We found that the amounts of VV and MPO+ clusters were strongly correlated; further, MPO+ clusters density was significantly associated with balloon-induced IH and increased at calciprotein particle-provoked endothelial dysfunction. Likewise, number and density of VV correlated with IH in bypass grafts for CABG surgery at the pre-intervention stage and were higher in venous conduits which more frequently suffered from IH as compared with arterial grafts. Collectively, our results underline the pathophysiological importance of excessive VV upon the vascular injury or at the exposure to cardiovascular risk factors, highlight MPO+ clusters as an informative marker of adventitial and perivascular inflammation, and propose another mechanistic explanation of a higher long-term patency of arterial grafts upon the CABG surgery. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

10 pages, 959 KiB  
Communication
TMAO Upregulates Members of the miR-17/92 Cluster and Impacts Targets Associated with Atherosclerosis
by Laura Díez-Ricote, Paloma Ruiz-Valderrey, Víctor Micó, Ruth Blanco, Joao Tomé-Carneiro, Alberto Dávalos, José M. Ordovás and Lidia Daimiel
Int. J. Mol. Sci. 2022, 23(20), 12107; https://doi.org/10.3390/ijms232012107 - 11 Oct 2022
Cited by 6 | Viewed by 2062
Abstract
Atherosclerosis is a hallmark of cardiovascular disease, and lifestyle strongly impacts its onset and progression. Nutrients have been shown to regulate the miR-17/92 cluster, with a role in endothelial function and atherosclerosis. Choline, betaine, and L-carnitine, found in animal foods, are metabolized into [...] Read more.
Atherosclerosis is a hallmark of cardiovascular disease, and lifestyle strongly impacts its onset and progression. Nutrients have been shown to regulate the miR-17/92 cluster, with a role in endothelial function and atherosclerosis. Choline, betaine, and L-carnitine, found in animal foods, are metabolized into trimethylamine (TMA) by the gut microbiota. TMA is then oxidized to TMAO, which has been associated with atherosclerosis. Our aim was to investigate whether TMAO modulates the expression of the miR-17/92 cluster, along with the impact of this modulation on the expression of target genes related to atherosclerosis and inflammation. We treated HepG-2 cells, THP-1 cells, murine liver organoids, and human peripheral mononuclear cells with 6 µM of TMAO at different timepoints. TMAO increased the expression of all analyzed members of the cluster, except for miR-20a-5p in murine liver organoids and primary human macrophages. Genes and protein levels of SERPINE1 and IL-12A increased. Both have been associated with atherosclerosis and cardiovascular disease (CDVD) and are indirectly modulated by the miR-17-92 cluster. We concluded that TMAO modulates the expression of the miR-17/92 cluster and that such modulation could promote inflammation through IL-12A and blood clotting through SERPINE1 expression, which could ultimately promote atherosclerosis and CVD. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

12 pages, 1127 KiB  
Article
Immuno-Mediated Inflammation in Hypertensive Patients with 1-h Post-Load Hyperglycemia
by Maria Perticone, Raffaele Maio, Simona Gigliotti, Franco Arturi, Elena Succurro, Angela Sciacqua, Francesco Andreozzi, Giorgio Sesti and Francesco Perticone
Int. J. Mol. Sci. 2022, 23(18), 10891; https://doi.org/10.3390/ijms231810891 - 17 Sep 2022
Cited by 1 | Viewed by 1514
Abstract
Inflammation plays a key role in the pathogenesis/progression of atherosclerosis, and inflammatory molecules contribute to the progression of cardiovascular disease. Subjects with normal post-load glucose tolerance and 1-h post-load plasma glucose >155 mg/dL have an increased risk of subclinical target organ damage and [...] Read more.
Inflammation plays a key role in the pathogenesis/progression of atherosclerosis, and inflammatory molecules contribute to the progression of cardiovascular disease. Subjects with normal post-load glucose tolerance and 1-h post-load plasma glucose >155 mg/dL have an increased risk of subclinical target organ damage and incident diabetes. We aimed to test possible differences in immune-mediated inflammatory parameters in newly-diagnosed hypertensives with or without 1-h post-load hyperglycemia. We enrolled 25 normotensives (NGT) and 50 hypertensives normotolerant on oral glucose tolerance test, further divided into two groups based on 1-h post-load plasma glucose: NGT 1-h ≥ 155 (n = 25) and NGT 1-h < 155 (n = 25). We measured toll-like receptor (TLR) 2, TLR4, nuclear factor kβ (NF-kβ), interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α. Hypertensives showed significantly worse metabolic and lipid profiles, and higher values of body mass ass index (BMI), creatinine, and inflammatory parameters, compared to controls. NGT 1-h ≥ 155 had a worse glycometabolic profile and higher values of TLR2 (9.4 ± 4.2 vs. 5.9 ± 2.6 MFI), TLR4 (13.1 ± 3.9 vs. 7.8 ± 2.3 MFI), NF-kβ (0.21 ± 0.07 vs. 0.14 ± 0.04), IL-1β (6.9 ± 3.4 vs. 3.2 ± 2.1 pg/mL), IL-6 (10.8 ± 2.6 vs. 4.1 ± 1.6 pg/mL), IL-8 (27.6 ± 9.3 vs. 13.3 ± 5.6 pg/mL), TNF-α (6.4 ± 2.9 vs. 3.3 ± 1.4 pg/mL), and high-sensitivity C-reactive protein (hs-CRP) (4.8 ± 1.5 vs. 2.7 ± 1.0 mg/dL) in comparison with NGT 1-h < 155. Matsuda-index and 1-h post-load glycemia were retained as major predictors of TLRs and NF-kβ. These results contribute to better characterizing cardiovascular risk in hypertensives. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

21 pages, 7018 KiB  
Article
Sex Differences in Coronary Artery Disease and Diabetes Revealed by scRNA-Seq and CITE-Seq of Human CD4+ T Cells
by Ryosuke Saigusa, Jenifer Vallejo, Rishab Gulati, Sujit Silas Armstrong Suthahar, Vasantika Suryawanshi, Ahmad Alimadadi, Jeffrey Makings, Christopher P. Durant, Antoine Freuchet, Payel Roy, Yanal Ghosheh, William Pandori, Tanyaporn Pattarabanjird, Fabrizio Drago, Angela Taylor, Coleen A. McNamara, Avishai Shemesh, Lewis L. Lanier, Catherine C. Hedrick and Klaus Ley
Int. J. Mol. Sci. 2022, 23(17), 9875; https://doi.org/10.3390/ijms23179875 - 30 Aug 2022
Cited by 8 | Viewed by 4034
Abstract
Despite the decades-old knowledge that males and people with diabetes mellitus (DM) are at increased risk for coronary artery disease (CAD), the reasons for this association are only partially understood. Among the immune cells involved, recent evidence supports a critical role of T [...] Read more.
Despite the decades-old knowledge that males and people with diabetes mellitus (DM) are at increased risk for coronary artery disease (CAD), the reasons for this association are only partially understood. Among the immune cells involved, recent evidence supports a critical role of T cells as drivers and modifiers of CAD. CD4+ T cells are commonly found in atherosclerotic plaques. We aimed to understand the relationship of CAD with sex and DM by single-cell RNA (scRNA-Seq) and antibody sequencing (CITE-Seq) of CD4+ T cells. Peripheral blood mononuclear cells (PBMCs) of 61 men and women who underwent cardiac catheterization were interrogated by scRNA-Seq combined with 49 surface markers (CITE-Seq). CAD severity was quantified using Gensini scores, with scores above 30 considered CAD+ and below 6 considered CAD−. Four pairs of groups were matched for clinical and demographic parameters. To test how sex and DM changed cell proportions and gene expression, we compared matched groups of men and women, as well as diabetic and non-diabetic subjects. We analyzed 41,782 single CD4+ T cell transcriptomes for sex differences in 16 women and 45 men with and without coronary artery disease and with and without DM. We identified 16 clusters in CD4+ T cells. The proportion of cells in CD4+ effector memory cluster 8 (CD4T8, CCR2+ Em) was significantly decreased in CAD+, especially among DM+ participants. This same cluster, CD4T8, was significantly decreased in female participants, along with two other CD4+ T cell clusters. In CD4+ T cells, 31 genes showed significant and coordinated upregulation in both CAD and DM. The DM gene signature was partially additive to the CAD gene signature. We conclude that (1) CAD and DM are clearly reflected in PBMC transcriptomes, and (2) significant differences exist between women and men and (3) between subjects with DM and non-DM. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

9 pages, 1029 KiB  
Article
High Plasma Levels of Fortilin in Patients with Coronary Artery Disease
by Masayuki Aoyama, Yoshimi Kishimoto, Emi Saita, Reiko Ohmori, Kojiro Tanimoto, Masato Nakamura, Kazuo Kondo and Yukihiko Momiyama
Int. J. Mol. Sci. 2022, 23(16), 8923; https://doi.org/10.3390/ijms23168923 - 10 Aug 2022
Cited by 2 | Viewed by 1667
Abstract
Excessive apoptosis is known to be a common feature of atherosclerotic lesions. Fortilin is recognized to have potent antiapoptotic properties. An increased fortilin expression was demonstrated in atherosclerotic lesions, and fortilin knockout mice developed less atherosclerosis. However, no study has reported blood fortilin [...] Read more.
Excessive apoptosis is known to be a common feature of atherosclerotic lesions. Fortilin is recognized to have potent antiapoptotic properties. An increased fortilin expression was demonstrated in atherosclerotic lesions, and fortilin knockout mice developed less atherosclerosis. However, no study has reported blood fortilin levels in patients with coronary artery disease (CAD). We investigated plasma fortilin levels in 384 patients undergoing coronary angiography. CAD severity was evaluated as the numbers of stenotic vessels and segments. CAD was found in 208 patients (one-vessel (1VD), n = 86; two-vessel (2VD), n = 68; and three-vessel disease (3VD), n = 54). Plasma C-reactive protein (CRP) levels were higher in patients with CAD than without CAD (median 0.60 vs. 0.45 mg/L, p < 0.01). Notably, fortilin levels were higher in patients with CAD than without CAD (75.1 vs. 69.7 pg/mL, p < 0.02). A stepwise increase in fortilin was found according to the number of stenotic vessels: 69.7 in CAD(−), 71.1 in 1VD, 75.7 in 2VD, and 84.7 pg/mL in 3VD (p < 0.01). Fortilin levels also correlated with the number of stenotic segments (r = 0.16) and CRP levels (r = 0.24) (p < 0.01). In a multivariate analysis, fortilin levels were independently associated with 3VD. The odds ratio for 3VD was 1.93 (95%CI = 1.01–3.71) for a high fortilin level (>70.0 pg/mL). Thus, plasma fortilin levels in patients with CAD, especially those with 3VD, were found to be high and to be associated with the severity of CAD. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

Review

Jump to: Editorial, Research

20 pages, 1089 KiB  
Review
Macrophage Phenotyping in Atherosclerosis by Proteomics
by Sonia Eligini, Erica Gianazza, Alice Mallia, Stefania Ghilardi and Cristina Banfi
Int. J. Mol. Sci. 2023, 24(3), 2613; https://doi.org/10.3390/ijms24032613 - 30 Jan 2023
Cited by 5 | Viewed by 2855
Abstract
Macrophages are heterogeneous and plastic cells, able to adapt their phenotype and functions to changes in the microenvironment. They are involved in several homeostatic processes and also in many human diseases, including atherosclerosis, where they participate in all the stages of the disease. [...] Read more.
Macrophages are heterogeneous and plastic cells, able to adapt their phenotype and functions to changes in the microenvironment. They are involved in several homeostatic processes and also in many human diseases, including atherosclerosis, where they participate in all the stages of the disease. For these reasons, macrophages have been studied extensively using different approaches, including proteomics. Proteomics, indeed, may be a powerful tool to better understand the behavior of these cells, and a careful analysis of the proteome of different macrophage phenotypes can help to better characterize the role of these phenotypes in atherosclerosis and provide a broad view of proteins that might potentially affect the course of the disease. In this review, we discuss the different proteomic techniques that have been used to delineate the proteomic profile of macrophage phenotypes and summarize some results that can help to elucidate the roles of macrophages and develop new strategies to counteract the progression of atherosclerosis and/or promote regression. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

29 pages, 1863 KiB  
Review
Cardiovascular Disease in Obstructive Sleep Apnea: Putative Contributions of Mineralocorticoid Receptors
by Mohammad Badran, Shawn B. Bender and David Gozal
Int. J. Mol. Sci. 2023, 24(3), 2245; https://doi.org/10.3390/ijms24032245 - 23 Jan 2023
Viewed by 3757
Abstract
Obstructive sleep apnea (OSA) is a chronic and highly prevalent condition that is associated with oxidative stress, inflammation, and fibrosis, leading to endothelial dysfunction, arterial stiffness, and vascular insulin resistance, resulting in increased cardiovascular disease and overall mortality rates. To date, OSA remains [...] Read more.
Obstructive sleep apnea (OSA) is a chronic and highly prevalent condition that is associated with oxidative stress, inflammation, and fibrosis, leading to endothelial dysfunction, arterial stiffness, and vascular insulin resistance, resulting in increased cardiovascular disease and overall mortality rates. To date, OSA remains vastly underdiagnosed and undertreated, with conventional treatments yielding relatively discouraging results for improving cardiovascular outcomes in OSA patients. As such, a better mechanistic understanding of OSA-associated cardiovascular disease (CVD) and the development of novel adjuvant therapeutic targets are critically needed. It is well-established that inappropriate mineralocorticoid receptor (MR) activation in cardiovascular tissues plays a causal role in a multitude of CVD states. Clinical studies and experimental models of OSA lead to increased secretion of the MR ligand aldosterone and excessive MR activation. Furthermore, MR activation has been associated with worsened OSA prognosis. Despite these documented relationships, there have been no studies exploring the causal involvement of MR signaling in OSA-associated CVD. Further, scarce clinical studies have exclusively assessed the beneficial role of MR antagonists for the treatment of systemic hypertension commonly associated with OSA. Here, we provide a comprehensive overview of overlapping mechanistic pathways recruited in the context of MR activation- and OSA-induced CVD and propose MR-targeted therapy as a potential avenue to abrogate the deleterious cardiovascular consequences of OSA. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

17 pages, 842 KiB  
Review
A Systematic Review and Meta-Analysis of Advanced Biomarkers for Predicting Incident Cardiovascular Disease among Asymptomatic Middle-Aged Adults
by Juan Luis Romero-Cabrera, Jacob Ankeny, Alejandro Fernández-Montero, Stefanos N. Kales and Denise L. Smith
Int. J. Mol. Sci. 2022, 23(21), 13540; https://doi.org/10.3390/ijms232113540 - 4 Nov 2022
Cited by 14 | Viewed by 3052
Abstract
Cardiovascular disease (CVD) continues as the most important cause of mortality. Better risk screening and prediction are needed to reduce the cardiovascular disease burden. The aim of the study was to assess the role of serum biomarkers in the prediction of CVD among [...] Read more.
Cardiovascular disease (CVD) continues as the most important cause of mortality. Better risk screening and prediction are needed to reduce the cardiovascular disease burden. The aim of the study was to assess the role of serum biomarkers in the prediction of CVD among asymptomatic middle-aged adults with no prior CVD history. A systematic review and meta-analysis were carried out using literature from PubMed and following PRISMA reporting guidelines. Twenty-five studies met our inclusion criteria and were included in the systematic review. The most commonly studied biomarker was high-sensitivity C reactive protein (hs-CRP) (10 studies), which showed that higher hs-CRP levels are associated with an increased risk of subsequent CVD events and mortality. In addition, several less-studied biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP), fibrinogen, gamma-glutamyl transferase (GGT), and others) also showed significant associations with greater future risk of CVD. A meta-analysis was possible to perform for hs-CRP and NT-proBNP, which showed statistically significant results for the ability of hs-CRP (hazard ratio (HR) 1.19, (95% CI: 1.09–1.30), p < 0.05) and NT-proBNP (HR 1.22, (1.13–1.32), p < 0.05) to predict incident CVD among middle-aged adults without a prior CVD history or symptoms. Several serum biomarkers, particularly hs-CRP and NT-proBNP, have the potential to improve primary CVD risk prevention among asymptomatic middle-aged adults. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

24 pages, 868 KiB  
Review
Targeting Immune Senescence in Atherosclerosis
by Danusha Michelle Vellasamy, Sin-Jye Lee, Khang Wen Goh, Bey-Hing Goh, Yin-Quan Tang, Long Chiau Ming and Wei Hsum Yap
Int. J. Mol. Sci. 2022, 23(21), 13059; https://doi.org/10.3390/ijms232113059 - 27 Oct 2022
Cited by 14 | Viewed by 4137
Abstract
Atherosclerosis is one of the main underlying causes of cardiovascular diseases (CVD). It is associated with chronic inflammation and intimal thickening as well as the involvement of multiple cell types including immune cells. The engagement of innate or adaptive immune response has either [...] Read more.
Atherosclerosis is one of the main underlying causes of cardiovascular diseases (CVD). It is associated with chronic inflammation and intimal thickening as well as the involvement of multiple cell types including immune cells. The engagement of innate or adaptive immune response has either athero-protective or atherogenic properties in exacerbating or alleviating atherosclerosis. In atherosclerosis, the mechanism of action of immune cells, particularly monocytes, macrophages, dendritic cells, and B- and T-lymphocytes have been discussed. Immuno-senescence is associated with aging, viral infections, genetic predispositions, and hyperlipidemia, which contribute to atherosclerosis. Immune senescent cells secrete SASP that delays or accelerates atherosclerosis plaque growth and associated pathologies such as aneurysms and coronary artery disease. Senescent cells undergo cell cycle arrest, morphological changes, and phenotypic changes in terms of their abundances and secretome profile including cytokines, chemokines, matrix metalloproteases (MMPs) and Toll-like receptors (TLRs) expressions. The senescence markers are used in therapeutics and currently, senolytics represent one of the emerging treatments where specific targets and clearance of senescent cells are being considered as therapy targets for the prevention or treatment of atherosclerosis. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

13 pages, 686 KiB  
Review
Non-Mouse Models of Atherosclerosis: Approaches to Exploring the Translational Potential of New Therapies
by Danielle Kamato, Iqra Ilyas, Suowen Xu and Peter J. Little
Int. J. Mol. Sci. 2022, 23(21), 12964; https://doi.org/10.3390/ijms232112964 - 26 Oct 2022
Cited by 3 | Viewed by 3131
Abstract
Cardiovascular disease is the largest single cause of disease-related mortality worldwide and the major underlying pathology is atherosclerosis. Atherosclerosis develops as a complex process of vascular lipid deposition and retention by modified proteoglycans, endothelial dysfunction and unresolved chronic inflammation. There are a multitude [...] Read more.
Cardiovascular disease is the largest single cause of disease-related mortality worldwide and the major underlying pathology is atherosclerosis. Atherosclerosis develops as a complex process of vascular lipid deposition and retention by modified proteoglycans, endothelial dysfunction and unresolved chronic inflammation. There are a multitude of current therapeutic agents, most based on lowering plasma lipid levels, but, overall, they have a lower than optimum level of efficacy and many deaths continue to arise from cardiovascular disease world-wide. To identify and evaluate potential novel cardiovascular drugs, suitable animal models that reproduce human atherosclerosis with a high degree of fidelity are required as essential pre-clinical research tools. Commonly used animal models of atherosclerosis include mice (ApoE−/−, LDLR−/− mice and others), rabbits (WHHL rabbits and others), rats, pigs, hamster, zebrafish and non-human primates. Models based on various wild-type and genetically modified mice have been extensively reviewed but mice may not always be appropriate. Thus, here, we provide an overview of the advantages and shortcomings of various non-mouse animal models of atherosclerotic plaque formation, and plaque rupture, as well as commonly used interventional strategies. Taken together, the combinatorial selection of suitable animal models readily facilitates reproducible and rigorous translational research in discovering and validating novel anti-atherosclerotic drugs. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

19 pages, 757 KiB  
Review
Non-Traditional Pro-Inflammatory and Pro-Atherosclerotic Risk Factors Related to Systemic Lupus Erythematosus
by Patricia Richter, Anca Cardoneanu, Ciprian Rezus, Alexandra Maria Burlui and Elena Rezus
Int. J. Mol. Sci. 2022, 23(20), 12604; https://doi.org/10.3390/ijms232012604 - 20 Oct 2022
Cited by 2 | Viewed by 1702
Abstract
Cardiovascular diseases (CVD) are one of the leading causes of high mortality in patients with systemic lupus erythematosus (SLE). The Framingham risk score and other traditional risk factors do not fully reflect the CVD risk in SLE patients. Therefore, in order to stratify [...] Read more.
Cardiovascular diseases (CVD) are one of the leading causes of high mortality in patients with systemic lupus erythematosus (SLE). The Framingham risk score and other traditional risk factors do not fully reflect the CVD risk in SLE patients. Therefore, in order to stratify these high-risk patients, additional biomarkers for subclinical CVD are needed. The mechanisms of atherogenesis in SLE are still being investigated. During the past decades, many reports recognized that inflammation plays a crucial role in the development of atherosclerosis. The aim of this report is to present novel proinflammatory and pro-atherosclerotic risk factors that are closely related to SLE inflammation and which determine an increased risk for the occurrence of early cardiovascular events. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

17 pages, 1278 KiB  
Review
Platelet-Derived Exosomes in Atherosclerosis
by Chiara Gardin, Letizia Ferroni, Sara Leo, Elena Tremoli and Barbara Zavan
Int. J. Mol. Sci. 2022, 23(20), 12546; https://doi.org/10.3390/ijms232012546 - 19 Oct 2022
Cited by 17 | Viewed by 2836
Abstract
Atherosclerosis (AS), the main cause of many cardiovascular diseases (CVDs), is a progressive inflammatory disease characterized by the accumulation of lipids, fibrous elements, and calcification in the innermost layers of arteries. The result is the thickening and clogging of these vessel walls. Several [...] Read more.
Atherosclerosis (AS), the main cause of many cardiovascular diseases (CVDs), is a progressive inflammatory disease characterized by the accumulation of lipids, fibrous elements, and calcification in the innermost layers of arteries. The result is the thickening and clogging of these vessel walls. Several cell types are directly involved in the pathological progression of AS. Among them, platelets represent the link between AS, inflammation, and thrombosis. Indeed, besides their pivotal role in hemostasis and thrombosis, platelets are key mediators of inflammation at injury sites, where they act by regulating the function of other blood and vascular cell types, including endothelial cells (ECs), leukocytes, and vascular smooth muscle cells (VSMCs). In recent years, increasing evidence has pointed to a central role of platelet-derived extracellular vesicles (P-EVs) in the modulation of AS pathogenesis. However, while the role of platelet-derived microparticles (P-MPs) has been significantly investigated in recent years, the same cannot be said for platelet-derived exosomes (P-EXOs). For this reason, this reviews aims at summarizing the isolation methods and biological characteristics of P-EXOs, and at discussing their involvement in intercellular communication in the pathogenesis of AS. Evidence showing how P-EXOs and their cargo can be used as biomarkers for AS is also presented in this review. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

18 pages, 1885 KiB  
Review
Molecular Mechanisms Underlying Pathological and Therapeutic Roles of Pericytes in Atherosclerosis
by Siarhei A. Dabravolski, Alexander M. Markin, Elena R. Andreeva, Ilya I. Eremin, Alexander N. Orekhov and Alexandra A. Melnichenko
Int. J. Mol. Sci. 2022, 23(19), 11663; https://doi.org/10.3390/ijms231911663 - 1 Oct 2022
Cited by 7 | Viewed by 2643
Abstract
Pericytes are multipotent mesenchymal stromal cells playing an active role in angiogenesis, vessel stabilisation, maturation, remodelling, blood flow regulation and are able to trans-differentiate into other cells of the mesenchymal lineage. In this review, we summarised recent data demonstrating that pericytes play a [...] Read more.
Pericytes are multipotent mesenchymal stromal cells playing an active role in angiogenesis, vessel stabilisation, maturation, remodelling, blood flow regulation and are able to trans-differentiate into other cells of the mesenchymal lineage. In this review, we summarised recent data demonstrating that pericytes play a key role in the pathogenesis and development of atherosclerosis (AS). Pericytes are involved in lipid accumulation, inflammation, growth, and vascularization of the atherosclerotic plaque. Decreased pericyte coverage, endothelial and pericyte dysfunction is associated with intraplaque angiogenesis and haemorrhage, calcification and cholesterol clefts deposition. At the same time, pericytes can be used as a novel therapeutic target to promote vessel maturity and stability, thus reducing plaque vulnerability. Finally, we discuss recent studies exploring effective AS treatments with pericyte-mediated anti-atherosclerotic, anti-inflammatory and anti-apoptotic effects. Full article
(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective 3.0)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-17
Back to TopTop