Atherosclerosis最新文献

{"title":"Discordance analyses comparing LDL cholesterol, Non-HDL cholesterol, and apolipoprotein B for cardiovascular risk estimation","authors":"Camilla Ditlev Lindhardt Johannesen ,&nbsp;Martin Bødtker Mortensen ,&nbsp;Børge Grønne Nordestgaard ,&nbsp;Anne Langsted","doi":"10.1016/j.atherosclerosis.2025.119139","DOIUrl":"10.1016/j.atherosclerosis.2025.119139","url":null,"abstract":"<div><div>For decades, studies have tried to identify the cholesterol marker that best reflects risk of atherosclerotic cardiovascular disease(ASCVD). Comparing low-density-lipoprotein(LDL) cholesterol, non-high-density-lipoprotein(non-HDL) cholesterol, and apolipoprotein B(apoB) as ASCVD risk markers has been challenged by high correlation between them. Thus, discordance analyses, directly addressing disagreements between the cholesterol markers, have emerged. Approaches adopted to define discordance originate in one of three methods: discordance by cut-points, discordance by percentiles, or discordance by residuals. Commonly, concordant lipid levels serve as reference examining the association between discordant lipid levels with risk of ASCVD. Importantly, concordant reference groups present heterogeneity of clinical relevance across different discordance methods as concordant low lipid levels associate with lowest ASCVD risk while concordant high lipid levels associate with highest risk. Thus, results from different discordance approaches cannot be directly compared. Moreover, discordance between cholesterol markers is more frequently seen in individuals treated with lipid-lowering medication than in individuals not treated with lipid-lowering medication. Accordingly, studies performing discordance analyses have reported inconsistent and even conflicting results. Discordance by cut-points appears the most intuitive and clinically applicable method; results from these analyses suggest that elevated LDL cholesterol, non-HDL cholesterol, or apoB levels in individuals not treated with lipid-lowering medication confer increased ASCVD risk while in individuals treated with lipid-lowering medication, elevated non-HDL cholesterol and apoB levels best indicate residual risk. Results from discordance analyses comparing LDL cholesterol, non-HDL cholesterol, and apoB in risk of ASCVD as well as complexities of discordance analyses and considerations regarding interpretations are discussed in this review.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"403 ","pages":"Article 119139"},"PeriodicalIF":4.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143591488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental pollutants and atherosclerosis: Epigenetic mechanisms linking genetic risk and disease.","authors":"Isabella Damiani, Elena Hurtado Solberg, Meghana Iyer, Paul Cheng, Chad S Weldy, Juyong Brian Kim","doi":"10.1016/j.atherosclerosis.2025.119131","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2025.119131","url":null,"abstract":"<p><p>Over the past half-century, significant strides have been made to identify key risk factors, genetic mechanisms, and treatments for atherosclerosis. Yet, coronary artery disease (CAD) remains a leading global public health challenge. While the heritability of CAD is well-documented, there is increasing focus on the role of environmental exposures, such as smoking, air pollution, and heavy metals, on global CAD risk. Recent research has shed light on the interplay between genetic variation and environmental factors, offering insights into gene-environment (GxE) interactions. Moreover, emerging evidence suggests that environmental toxicants can profoundly impact the epigenome, altering gene regulation beyond the genetic sequence itself, revealing novel mechanisms underlying disease. Epigenetic changes - such as modifications in DNA methylation, chromatin structure, and non-coding RNA function - are now recognized as key molecular determinants of atherosclerosis. These observations have created a foundational paradigm that environment, genetics, and epigenetic mechanisms influence risk through a highly complex interaction regulating cellular phenotype, pathology, and disease progression. In this review, we explore the mechanisms by which environmental exposures influence the epigenome and contribute to the regulation of atherosclerotic disease. Additionally, we examine the transgenerational epigenetic effects of these exposures on disease risk. Advancing our understanding of these mechanisms is essential for informing public health strategies aimed at mitigating harmful environmental exposures and reducing the global burden of cardiovascular disease.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119131"},"PeriodicalIF":4.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing atherosclerosis research: The Power of lipid imaging with MALDI-MSI.","authors":"Christoph H M Bookmeyer, F Xavier Correig, Luis Masana, Paolo Magni, Óscar Yanes, Maria Vinaixa","doi":"10.1016/j.atherosclerosis.2025.119130","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2025.119130","url":null,"abstract":"<p><p>Atherosclerosis is a chronic inflammatory disease that is one of the leading causes of mortality globally. It is characterized by the formation of atheromatous plaques in the intima layer of larger arteries. The (fibro-)fatty plaques usually develop asymptomatically within the vessel until a serious event such as myocardial infarction or stroke occurs. Lipids play a pivotal role in disease progression, but while the causal role of cholesterol is beyond doubt, the distribution of numerous other lipids within the heterogeneous layers of atherosclerotic plaques, and their biological function remain unclear. A deeper understanding of the pathophysiological progression of the disease for prognostics, diagnostics, treatment, and prevention is of great need. Mass spectrometry imaging (MSI), in particular with matrix-assisted laser desorption/ionization (MALDI) offers an unprecedented untargeted characterization of the physiological microenvironment, unraveling the spatial distribution of numerous biochemical compounds. MALDI-MSI offers an advantageous balance of sample preparation, chemical sensitivity, and spatial resolution, and thus has been established as a key technology in modern biomedical analysis. This review focuses on the analysis of lipids in atherosclerotic lesions with MALDI-MSI, for which the past years showed major developments in the spatial characterization of lipids and their interaction within atherosclerotic plaques. We will cover main contributions with a focus on the recent decade, elaborate possibilities, limitations, main findings, and recent developments from sample handling to instrumentation, and estimate current challenges and potentials of MALDI-MSI with respect to a clinical application.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119130"},"PeriodicalIF":4.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remnant Cholesterol: A Missed Opportunity in Cardiovascular Risk Reduction?","authors":"Luiz Sérgio Fernandes de Carvalho, Renato de Carvalho Barros","doi":"10.1016/j.atherosclerosis.2025.119129","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2025.119129","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119129"},"PeriodicalIF":4.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative analysis of single-cell transcriptomics and genetic associations identify cell states associated with vascular disease","authors":"Mark E. Pepin ,&nbsp;William E. Schwartzman ,&nbsp;Shi Fang ,&nbsp;Shamsudheen K. Vellarikkal ,&nbsp;Deepak S. Atri ,&nbsp;Ankith Reddy ,&nbsp;Qiaohan Xu ,&nbsp;Andrew R. Hamel ,&nbsp;Marie Billaud ,&nbsp;Ayellet V. Segrè ,&nbsp;Rajat M. Gupta","doi":"10.1016/j.atherosclerosis.2025.119108","DOIUrl":"10.1016/j.atherosclerosis.2025.119108","url":null,"abstract":"<div><h3>Background</h3><div>Vascular diseases are accompanied by alterations in cellular phenotypes which underlie disease pathogenesis, with single-cell technologies aiding in the discovery of cellular heterogeneity among endothelial cell (EC) and vascular smooth muscle cell (VSMC) populations. In atherosclerotic disease, VSMCs are hypothesized to transition between contractile and synthetic states; however, the specific vascular subpopulations and intermediate cell states responsible for early vascular dysfunction remain unclear.</div></div><div><h3>Methods</h3><div>We integrated newly generated and published single-nuclear RNA-sequencing (snRNA-seq) datasets to analyze normal (n = 7), aneurysmal (n = 9), and atherosclerotic (n = 2) flash-frozen human ascending thoracic aortas. Cell types and subtypes were defined using both top marker genes and canonical gene markers. Disease enrichment and relevant cell types were identified using newly developed computational tools to integrate GWAS data from multiple vascular disease-relevant studies with the single nuclei aortic expression profiles.</div></div><div><h3>Results</h3><div>Nuclear dissociation and snRNA-seq identified ten distinct transcriptomic clusters from the integrated analysis representing all major vascular cell populations. Three distinct VSMC populations emerged that exhibited differential expression of extracellular matrix, contractile and pro-proliferative genes. Aneurysmal specimens were enriched for one fibroblast and one VSMC subpopulation compared to healthy tissue. RNA-trajectory analysis inferred a phenotypic continuum of gene expression between VSMC A and VSMC B or C and between two of the identified fibroblast types. VSMCs and Fibroblast C exhibited the greatest cell type-specific enrichment of genes mapped to GWAS loci for coronary artery disease (CAD), blood pressure, and migraine. Cell type-specific enrichment scores were more robust among the transcriptional profiles from non-diseased vascular tissue.</div></div><div><h3>Conclusions</h3><div>Our use of single-cell isolation and new computational methods prioritizes the cell types that most contribute to vascular disease pathogenesis. Specifically, tissue dissociation and single-nuclear transcriptomics better represent all vascular cell types, from which we demonstrate enrichment of pro-proliferative VSMCs in TAA and further implicate phenotypic switching as a likely pathologic mechanism. Integrated analysis of cell-specific gene expression and vascular disease GWAS data implicate genes and pathways associated with fibroblast and VSMC cell-state transitions.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"403 ","pages":"Article 119108"},"PeriodicalIF":4.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA splicing of the STAT3 by PCBP1 promotes vulnerable plaque formation via macrophage-like phenotype modulation of vascular smooth muscle cell","authors":"Guobin Cheng ,&nbsp;Chengxu Sui ,&nbsp;Youyao Xu ,&nbsp;Wei Lu ,&nbsp;Xiaoyang Li","doi":"10.1016/j.atherosclerosis.2025.119128","DOIUrl":"10.1016/j.atherosclerosis.2025.119128","url":null,"abstract":"<div><h3>Background</h3><div>The increase of macrophage-like vascular smooth muscle cells (VSMCs) within atherosclerotic plaques significantly contributes to plaque vulnerability. The STAT3 signaling is crucial in maintaining the contractile phenotype of VSMCs. Recent studies have identified two isoforms of STAT3, STAT3α and STAT3β, generated through alternative splicing. However, the roles of these isoforms in VSMC phenotypic transformation and plaque vulnerability are not yet clear.</div></div><div><h3>Methods</h3><div>In this study, we examined the differential expression of STAT3α and STAT3β in vulnerable and stable plaque tissues, and their correlation with the content of macrophage-like VSMCs. Utilizing in vivo and in vitro experiments, we elucidated the regulatory mechanisms of STAT3 alternative splicing and the molecular mechanisms by which STAT3β induces the transformation of VSMCs into the macrophage-like phenotype.</div></div><div><h3>Results</h3><div>We observed a significant upregulation of STAT3β within macrophage-like VSMCs in vulnerable plaque tissues. Upregulation of STAT3β, not merely the downregulation of STAT3α, drives the transformation of VSMCs into the macrophage-like phenotype. The splicing factor PCBP1 binds to exon 23 of the STAT3 gene, suppressing the expression of STAT3β. Furthermore, STAT3β negatively regulates the expression of the acetyltransferase enzyme KAT2B, which in turn, inhibits the key transcription factor KLF4 associated with the macrophage-like phenotype.</div></div><div><h3>Conclusion</h3><div>Our findings provide insights into the role of STAT3β isoforms in plaque stability and the phenotypic flexibility of VSMCs, highlighting potential targets for therapeutic intervention in atherosclerosis.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"402 ","pages":"Article 119128"},"PeriodicalIF":4.9,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143378491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulatory miRNAs in essential hypertension","authors":"Daria Kostiniuk ,&nbsp;Saara Marttila ,&nbsp;Emma Raitoharju","doi":"10.1016/j.atherosclerosis.2024.119069","DOIUrl":"10.1016/j.atherosclerosis.2024.119069","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are short non-coding RNAs, that regulate gene-expression at post-transcriptional level. Unlike other RNA species, blood miRNAs circulate in a highly stable form, either within extracellular vesicles or bound to proteins. In recent years, circulatory miRNA profiles have been proposed as potential biomarkers for multitude of pathologies, including essential hypertension. However, the evidence of miRNA biomarker potential is limited, mainly due to the scarcity of profiling studies associating miRNA levels with hypertension. Furthermore, most of these studies have been performed with preselected miRNA pool, limiting their discovery potential. Here, we summarize the results of the unbiased profiling studies and additionally discuss findings from targeted miRNA analysis.</div><div>Only miR-30e has been found to be associated with hypertension in more than one unbiased study. The targeted analyses highlight the association of miR-1, -21, −34a, −92a, −122, −126, −143, −145, −605, −623, −1299, as well as let-7 and miR-30 families with hypertension. Current literature indicates that some of these miRNAs are involved in hypertension-associated vascular dysfunction and the development of atherosclerosis, suggesting a novel mechanism for cardiovascular disease risk posed by hypertension. All in all, studies associating hypertension with circulatory miRNA profiles are scarce, with several limitations affecting the comparability of the studies. This review discusses the functions and potential mechanisms linking the identified miRNAs to hypertension and underscores the need for further research.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"Article 119069"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic regulation of vascular smooth muscle cell phenotypes in atherosclerosis","authors":"Jordi Lambert,&nbsp;Helle F. Jørgensen","doi":"10.1016/j.atherosclerosis.2024.119085","DOIUrl":"10.1016/j.atherosclerosis.2024.119085","url":null,"abstract":"<div><div>Vascular smooth muscle cells (VSMCs) in adult arteries maintain substantial phenotypic plasticity, which allows for the reversible cell state changes that enable vascular remodelling and homeostasis. In atherosclerosis, VSMCs dedifferentiate in response to lipid accumulation and inflammation, resulting in loss of their characteristic contractile state. Recent studies showed that individual, pre-existing VSMCs expand clonally and can acquire many different phenotypes in atherosclerotic lesions. The changes in gene expression underlying this phenotypic diversity are mediated by epigenetic modifications which affect transcription factor access and thereby gene expression dynamics. Additionally, epigenetic mechanisms can maintain cellular memory, potentially facilitating reversion to the contractile state. While technological advances have provided some insight, a comprehensive understanding of how VSMC phenotypes are governed in disease remains elusive. Here we review current literature in light of novel insight from studies at single-cell resolution. We also discuss how lessons from epigenetic studies of cellular regulation in other fields could help in translating the potential of targeting VSMC phenotype conversion into novel therapies in cardiovascular disease.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"Article 119085"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of a machine learning-based metabolic marker for coronary artery disease in the UK Biobank","authors":"Kyle Gibson ,&nbsp;Iain S. Forrest ,&nbsp;Ben O. Petrazzini ,&nbsp;Áine Duffy ,&nbsp;Joshua K. Park ,&nbsp;Waqas Malick ,&nbsp;Robert S. Rosenson ,&nbsp;Ghislain Rocheleau ,&nbsp;Daniel M. Jordan ,&nbsp;Ron Do","doi":"10.1016/j.atherosclerosis.2024.119103","DOIUrl":"10.1016/j.atherosclerosis.2024.119103","url":null,"abstract":"<div><h3>Background and aims</h3><div>An <em>in silico</em> quantitative score of coronary artery disease (ISCAD), built using machine learning and clinical data from electronic health records, has been shown to result in gradations of risk of subclinical atherosclerosis, coronary artery disease (CAD) sequelae, and mortality. Large-scale metabolite biomarker profiling provides increased portability and objectivity in machine learning for disease prediction and gradation. However, these models have not been fully leveraged. We evaluated a quantitative score of CAD derived from probabilities of a machine learning model trained on metabolomic data.</div></div><div><h3>Methods</h3><div>We developed a CAD-predictive learning model using metabolic data from 93,642 individuals from the UK Biobank (median [IQR] age, 57 [14] years; 39,796 [42 %] male; 5640 [6 %] with diagnosed CAD), and assessed its probabilities as a quantitative metabolic risk score for CAD (M-CAD; range 0 [lowest probability] to 1 [highest probability]) in participants of the UK Biobank. The relationship of M-CAD with arterial stiffness index, ejection fraction, CAD sequelae, and mortality was assessed.</div></div><div><h3>Results</h3><div>The model predicted CAD with an area under the receiver-operating-characteristic curve of 0.712. Arterial Stiffness Index increased by 0.19 and ejection fraction decreased by 0.2 % per 0.1 increase in M-CAD. Both incident and recurrent myocardial infarction increased stepwise over M-CAD quartiles (odds ratio (OR) 15.3 [4.2 %] and 12.5 [0.2 %]) in top quartiles as compared to the first quartile of incident and recurrent MI respectively). Likewise, the hazard ratio and prevalence of all-cause mortality, CVD-associated mortality, and CAD-associated mortality increased stepwise over M-CAD deciles (2.98 [14 %], 9.34 [4.3 %], 26.7 [2.7 %] in the top deciles as compared to the first decile of all-cause, CVD, and CAD mortality respectively).</div></div><div><h3>Conclusions</h3><div>Metabolic-based machine learning can be used to build a quantitative risk score for CAD that is associated with atherosclerotic burden, CAD sequelae and mortality.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"Article 119103"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New options for young people with dyslipidemia: The future is bright!","authors":"Pierre Sabouret ,&nbsp;Marco Bernardi ,&nbsp;Elad Asher","doi":"10.1016/j.atherosclerosis.2024.119095","DOIUrl":"10.1016/j.atherosclerosis.2024.119095","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"Article 119095"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}