Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Atherosclerosis: From Molecular Biology to Therapeutic Perspective: 6th Edition

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

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 (30 October 2025) | Viewed by 24398

Share This Special Issue

Special Issue Editor

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

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 Perspective 6.0” 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
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 250 words) can be sent to the Editorial Office for assessment.

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

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (9 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

20 pages, 882 KB

Open AccessArticle

Sex and APOE ε2 Interactive Effects on the Longitudinal Change in Cognition in a Population-Based Cohort of Older Adults with Vascular Risk Factors

by Noemí Lamonja-Vicente, Rosalía Dacosta-Aguayo, Jorge López-Olóriz, Laia Prades-Senovilla, Juan José Soriano-Raya, Inmaculada C. Clemente, Júlia Miralbell, Maite Barrios, Elena López-Cancio, Cynthia Cáceres, Mónica Millán, Pere Torán, Guillem Pera, Meritxell Carmona-Cervelló, Cecilia Herrero, Pilar Montero-Alia, Maria Palau-Antoja, Maria Hernández-Pérez, Tamara Canento, Ana Gonzalez Fuxa, Maria Mataró and Marc Via Show full author list Hide full author list

Int. J. Mol. Sci. 2025, 26(21), 10591; https://doi.org/10.3390/ijms262110591 - 30 Oct 2025

Viewed by 498

Abstract

Cognitive aging trajectories differ widely across individuals, and genetic factors such as APOE and BDNF polymorphisms may contribute to this variability. While APOE ε4 has been widely studied, the influence of APOE ε2, particularly in interaction with sex, remains underexplored. This study aims to examine the longitudinal trajectory of APOE ε2 individuals on cognitive performance, and their interactions with sex, age, and BDNF Val66Met polymorphism, in a population-based cohort of older adults with vascular risk. We analyzed data from 386 participants (mean age: 71.8) from the Barcelona-AsIA Neuropsychology Study, followed over a 7-year period. Verbal memory, verbal fluency, and visuospatial domains were assessed. Linear regression models tested associations between cognitive change and genotypes, controlling for age, sex, education, depression, and vascular risk. Interaction terms and permutation testing were applied. Regression to the mean (RTM) effects were assessed. BDNF showed no significant associations with cognitive performance. RTM effects were evident across subgroups, particularly among ε2 carriers, suggesting this phenomenon partly explains the divergent results over time. APOE ε2 does not confer a consistent protective effect on cognition over time. Our results highlight that APOE ε2 may be detrimental to verbal memory in aging males. Full article

(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective: 6th Edition)

► Show Figures

Figure 1

15 pages, 1507 KB

Open AccessArticle

Integrative Transcriptomic and Epigenomic Profiling for Signature Identification in Coronary Artery Disease: A Pilot Study

by Mario Zanfardino, Anna D’Agostino, Ilaria Leone, Katia Pane, Chiara Caselli, Danilo Neglia, Bruna Punzo, Carlo Cavaliere, Andrea Soricelli and Monica Franzese

Int. J. Mol. Sci. 2025, 26(21), 10437; https://doi.org/10.3390/ijms262110437 - 27 Oct 2025

Viewed by 620

Abstract

Coronary Artery Disease (CAD), mainly due to the progressive development of atherosclerotic plaques, is one of the world’s leading causes of mortality and morbidity. A significant percentage of initial events (around 30%) remain fatal to this day despite significant advances in the diagnosis and treatment of cardiovascular diseases (CVDs). Early detection and risk stratification are therefore essential. In this study, we adopted a multi-omics approach integrating transcriptomic (RNA-seq) and epigenomic (ATAC-seq) profiling of peripheral blood mononuclear cells (PBMCs) from a cohort of individuals undergoing clinically indicated cardiac computed tomography angiography (CCTA) to uncover potential novel molecular markers of CAD. We identified 39 genes consistently dysregulated across all CAD subtypes. ATAC-seq analysis revealed distinct chromatin accessibility patterns at CAD-associated loci, with a predominance of quiescent and transcriptionally active states. Validation in an independent cohort confirmed the expression patterns of key Differentially Expressed Genes (DEGs), such as Claudin 18 (CLDN18), supporting the robustness of our findings. Consequently, the integration of multi-omics data allowed us to identify a core gene signature and regulatory patterns associated with disease severity, offering potential biomarkers for clinical risk stratification in patients with CAD. Full article

(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective: 6th Edition)

► Show Figures

Graphical abstract

19 pages, 4008 KB

Open AccessArticle

A Plasma Extracellular Vesicle-Derived microRNA Signature as a Potential Biomarker for Subclinical Coronary Atherosclerosis

by Mario Peña-Peña, Óscar Zepeda-García, Rosalinda Posadas-Sánchez, Fausto Sánchez-Muñoz, Mayra Domínguez-Pérez, Juan Alfonso Martínez-Greene, Fabiola López-Bautista, Adrián Hernández-Díazcouder, Rogelio F. Jiménez-Ortega, Alejandra Idan Valencia-Cruz, Adrián Nuñez-Salgado, Isaac Emanuel Mani-Arellano, Karina Martínez-Flores, Teresa Villarreal-Molina, Eduardo Martínez-Martínez and Leonor Jacobo-Albavera

Int. J. Mol. Sci. 2025, 26(17), 8727; https://doi.org/10.3390/ijms26178727 - 7 Sep 2025

Cited by 1 | Viewed by 2133

Abstract

Subclinical coronary atherosclerosis (SCA) is an early stage of coronary artery disease (CAD) that often goes unrecognized until clinical events occur. Identifying circulating molecular biomarkers could improve early diagnosis and risk assessment in asymptomatic individuals. This study employed a two-phase approach to identify plasma extracellular vesicle (EV)-derived microRNAs (miRNAs) associated with SCA. In the discovery phase, plasma samples from male participants were analyzed using Affymetrix GeneChip miRNA 4.0 microarrays. Differentially expressed miRNAs were refined through bioinformatic analysis, cross-species comparison with murine data, and target gene prediction. In the validation phase, six candidate miRNAs were quantified by RT-qPCR in an independent cohort. Six miRNAs were differentially expressed between individuals with SCA and controls. Among these, the combination of miR-146b-5p, miR-4701-3p, and miR-1180-3p demonstrated a high discriminative capacity for SCA (AUC = 0.8281; sensitivity = 93.75%; specificity = 93.75%). Functional enrichment analysis revealed that predicted target genes are involved in key atherosclerosis-related pathways, including inflammation, lipid metabolism, and vascular remodeling. EV-derived miRNAs may serve as non-invasive biomarkers for the early detection of coronary atherosclerosis. These findings provide insight into the molecular processes underlying subclinical vascular disease and support the integration of EV-associated miRNAs into preventive cardiology strategies. Full article

(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective: 6th Edition)

► Show Figures

Graphical abstract

17 pages, 663 KB

Open AccessArticle

The Association of Adropin with Asymptomatic Coronary Calcification in Patients in Early Stages of Chronic Kidney Disease

by Tetiana A. Berezina, Oleksandr O. Berezin, Evgen V. Novikov and Alexander E. Berezin

Int. J. Mol. Sci. 2025, 26(16), 7816; https://doi.org/10.3390/ijms26167816 - 13 Aug 2025

Cited by 1 | Viewed by 894

Abstract

Early stages of chronic kidney disease (CKD) are closely associated with vascular remodeling and coronary artery calcification. The aim of this study is to determine whether adropin is associated with asymptomatic coronary calcification in patients in the early stages of CKD. This study enrolled 337 individuals fulfilling the inclusion criteria of the early stages of CKD (G1–2, A1–3) and divided them into two subgroups with (n = 196) and without (n = 141) asymptomatic coronary artery calcification. Native coronary multi-detector computed tomography angiography was conducted to determine coronary artery calcification, which was stratified into four grades according to the Agatston method. Serum levels of adropin were measured by ELISA. The patients with known asymptomatic coronary artery calcification had significantly lower levels of adropin than those without this condition. The levels of adropin in individuals with mild (130–199 HU), moderate (200–299 HU), severe (300–399 HU) and very severe (≥400 HU) calcification were 3.13 (95% CI = 1.92–4.21) ng/mL, 2.3 (95% CI = 1.45–3.6) ng/mL, 2.1 (95% CI = 1.22–3.25) ng/mL and 1.26 (95% CI = 1.13–1.98) ng/mL, respectively. In multivariate logistic regression low adropin (<2.95 ng/mL), a presence of hypertension, type 2 diabetes mellitus (T2DM) exerted their independent potencies to predict asymptomatic coronary calcification. Moreover, adropin demonstrated better discriminative potency than concomitant hypertension and T2DM. Conclusions: Low levels of circulating adropin significantly predicted a risk of coronary artery calcification in patients in the early stages of CKD. Full article

(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective: 6th Edition)

► Show Figures

Figure 1

13 pages, 904 KB

Open AccessArticle

by Adam Płoński, Anna Krupa, Adam Filip Płoński, Dariusz Pawlak, Marcin Gabriel, Beata Sieklucka, Jerzy Głowiński and Krystyna Pawlak

Int. J. Mol. Sci. 2025, 26(10), 4731; https://doi.org/10.3390/ijms26104731 - 15 May 2025

Viewed by 884

Abstract

Atherosclerosis is a major contributor to ischemic stroke. Carotid plaque instability is a critical determinant of cerebrovascular events, yet its identification remains challenging. One chemokine with well-documented proatherogenic properties is MCP-1, whose levels are elevated in patients with conditions such as hypertension, obesity, and atherosclerosis. This study evaluated the association between obesity, serum MCP-1 levels, and carotid plaque instability as determined by ultrasound gray-scale median (GSM) analysis in 77 patients who underwent carotid endarterectomy. Patients were classified by body mass index. Serum MCP-1 concentrations were measured using the enzyme-linked immunosorbent assay technique. Analyses were performed to explore relationships between clinical parameters, biochemical markers, and plaque stability. Increasing body weight was paralleled by higher MCP-1 levels and lower GSM values, indicative of unstable plaques. Moreover, logistic regression analysis identified MCP-1 as one of the independent predictors of plaque instability, particularly in overweight and hypertensive patients. These results indicate the potential usefulness of MCP-1 as a biomarker of carotid plaque instability, confirming the negative effect of obesity in promoting other known cardiovascular risk factors causing plaque instability in patients with carotid atherosclerosis. Full article

(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective: 6th Edition)

► Show Figures

Figure 1

14 pages, 2215 KB

Open AccessArticle

Influence of Atherosclerosis-Associated Risk Factors on Expression of Endothelin Receptors in Advanced Atherosclerosis

by Oliver Herbers, Carsten Höltke, Marco Virgilio Usai, Jana Hochhalter, Moushami Mallik, Moritz Wildgruber, Anne Helfen and Miriam Stölting

Int. J. Mol. Sci. 2025, 26(5), 2310; https://doi.org/10.3390/ijms26052310 - 5 Mar 2025

Viewed by 1016

Abstract

Endothelin-1 (ET-1) levels are altered in atherosclerosis, while the roles of the endothelin receptors ET_AR and ET_BR during the pathogenesis of atherosclerosis remain unclear. Therefore, the focus of this study was to clarify how endothelin receptors are expressed in advanced human atherosclerotic plaques and how this is related to atherosclerotic risk factors. Ex vivo expression analysis was performed by quantitative real-time PCR (qRT-PCR) of 98 atherosclerotic plaques and controls that were obtained from adult patients undergoing vascular surgery. Correlation analyses of atherosclerosis-promoting factors were accomplished using a linear regression model. We found an overall reduced expression of ET receptors and smooth muscle actin (SMA), a marker of healthy vascular smooth muscle cells, in atherosclerotic plaques, whereas the levels of ET-1 and matrix metalloproteinase 2 (MMP-2), a marker of atherosclerosis progression, remained unchanged. Reduced expression was predominantly correlated with hypertension, which affects both receptors as well as SMA. Age, body mass index (BMI) and gender also correlated with either ET_AR, ET_BR or SMA expression in advanced plaques. In contrast, no effect of diabetes mellitus or smoking was found, indicating an ancillary effect of those risk factors. The results of our study indicate that endothelin receptor expression during the pathogenesis of atherosclerosis is predominantly correlated with hypertension. Full article

(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective: 6th Edition)

► Show Figures

Figure 1

13 pages, 2682 KB

Open AccessArticle

Glucose-Dependent Insulinotropic Polypeptide Inhibits AGE-Induced NADPH Oxidase-Derived Oxidative Stress Generation and Foam Cell Formation in Macrophages Partly via AMPK Activation

by Michishige Terasaki, Hironori Yashima, Yusaku Mori, Tomomi Saito, Naoto Inoue, Takanori Matsui, Naoya Osaka, Tomoki Fujikawa, Makoto Ohara and Sho-ichi Yamagishi

Int. J. Mol. Sci. 2024, 25(17), 9724; https://doi.org/10.3390/ijms25179724 - 8 Sep 2024

Cited by 7 | Viewed by 2235

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) of the incretin group has been shown to exert pleiotropic actions. There is growing evidence that advanced glycation end products (AGEs), senescent macromolecules formed at an accelerated rate under chronic hyperglycemic conditions, play a role in the pathogenesis of atherosclerotic cardiovascular disease in diabetes. However, whether and how GIP could inhibit the AGE-induced foam cell formation of macrophages, an initial step of atherosclerosis remains to be elucidated. In this study, we address these issues. We found that AGEs increased oxidized low-density-lipoprotein uptake into reactive oxygen species (ROS) generation and Cdk5 and CD36 gene expressions in human U937 macrophages, all of which were significantly blocked by [D-Ala²]GIP(1–42) or an inhibitor of NADPH oxidase activity. An inhibitor of AMP-activated protein kinase (AMPK) attenuated all of the beneficial effects of [D-Ala²]GIP(1–42) on AGE-exposed U937 macrophages, whereas an activator of AMPK mimicked the effects of [D-Ala²]GIP(1–42) on foam cell formation, ROS generation, and Cdk5 and CD36 gene expressions in macrophages. The present study suggests that [D-Ala²]GIP(1–42) could inhibit the AGE-RAGE-induced, NADPH oxidase-derived oxidative stress generation in U937 macrophages via AMPK activation and subsequently suppress macrophage foam cell formation by reducing the Cdk5-CD36 pathway. Full article

(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective: 6th Edition)

► Show Figures

Figure 1

Review

Jump to: Research

32 pages, 1002 KB

Open AccessReview

Atherosclerosis and the Bidirectional Relationship Between Cancer and Cardiovascular Disease: From Bench to Bedside, Part 2 Management

by Giuseppina Gallucci, Mario Larocca, Alessandro Navazio, Fabio Maria Turazza, Alessandro Inno, Maria Laura Canale, Stefano Oliva, Giulia Besutti, Andrea Tedeschi, Daniela Aschieri, Antonio Russo, Stefania Gori, Nicola Silvestris, Carmine Pinto and Luigi Tarantini

Int. J. Mol. Sci. 2025, 26(1), 334; https://doi.org/10.3390/ijms26010334 - 2 Jan 2025

Cited by 5 | Viewed by 2890

Abstract

The first part of this review highlighted the evolving landscape of atherosclerosis, noting emerging cardiometabolic risk factors, the growing impact of exposomes, and social determinants of health. The prominent role of atherosclerosis in the bidirectional relationship between cardiovascular disease and cancer was also discussed. In this second part, we examine the complex interplay between multimorbid cardio-oncologic patients, cardiometabolic risk factors, and the harmful environments that lend a “syndemic” nature to these chronic diseases. We summarize management strategies targeting disordered cardiometabolic factors to mitigate cardiovascular disease and explore molecular mechanisms enabling more tailored therapies. Importantly, we emphasize the early interception of atherosclerosis through multifactorial interventions that detect subclinical signs (via biomarkers and imaging) to treat modifiable risk factors and prevent clinical events. A concerted preventive effort—referred to by some as a “preventome”—is essential to reduce the burden of atherosclerosis-driven chronic diseases, shifting from mere chronic disease management to the proactive promotion of “chronic health”. Full article

(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective: 6th Edition)

► Show Figures

Figure 1

22 pages, 6116 KB

Open AccessReview

The Implications of Aging on Vascular Health

by Bulbul Ahmed, Ahmed A. Rahman, Sujin Lee and Rajeev Malhotra

Int. J. Mol. Sci. 2024, 25(20), 11188; https://doi.org/10.3390/ijms252011188 - 17 Oct 2024

Cited by 39 | Viewed by 11738

Abstract

Vascular aging encompasses structural and functional changes in the vasculature, significantly contributing to cardiovascular diseases, which are the leading cause of death globally. The incidence and prevalence of these diseases increase with age, with most morbidity and mortality attributed to myocardial infarction and stroke. Diagnosing and intervening in vascular aging while understanding the mechanisms behind age-induced vascular phenotypic and pathophysiological alterations offers the potential for delaying and preventing cardiovascular mortality in an aging population. This review delves into various aspects of vascular aging by examining age-related changes in arterial health at the cellular level, including endothelial dysfunction, cellular senescence, and vascular smooth muscle cell transdifferentiation, as well as at the structural level, including arterial stiffness and changes in wall thickness and diameter. We also explore aging-related changes in perivascular adipose tissue deposition, arterial collateralization, and calcification, providing insights into the physiological and pathological implications. Overall, aging induces phenotypic changes that augment the vascular system’s susceptibility to disease, even in the absence of traditional risk factors, such as hypertension, diabetes, obesity, and smoking. Overall, age-related modifications in cellular phenotype and molecular homeostasis increase the vulnerability of the arterial vasculature to structural and functional alterations, thereby accelerating cardiovascular risk. Increasing our understanding of these modifications is crucial for success in delaying or preventing cardiovascular diseases. Non-invasive techniques, such as measuring carotid intima-media thickness, pulse wave velocity, and flow-mediated dilation, as well as detecting vascular calcifications, can be used for the early detection of vascular aging. Targeting specific pathological mechanisms, such as cellular senescence and enhancing angiogenesis, holds promise for innovative therapeutic approaches. Full article

(This article belongs to the Special Issue Atherosclerosis: From Molecular Biology to Therapeutic Perspective: 6th Edition)

► Show Figures

Journal Menu

Journal Browser

Atherosclerosis: From Molecular Biology to Therapeutic Perspective: 6th Edition

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (9 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI