Atherosclerosis最新文献

{"title":"Residual cardiovascular risk in CKD: Reevaluating remnant cholesterol and inflammation","authors":"Haiting Huang, Guirong Dong","doi":"10.1016/j.atherosclerosis.2025.120453","DOIUrl":"10.1016/j.atherosclerosis.2025.120453","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"410 ","pages":"Article 120453"},"PeriodicalIF":5.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079566","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":"Sex Differences and similarities in the Management of Familial Hypercholesterolemia during life course: learning from the younglings","authors":"Mariko Harada-Shiba MD, PhD , Raul D. Santos MD, PhD, MSc","doi":"10.1016/j.atherosclerosis.2025.120518","DOIUrl":"10.1016/j.atherosclerosis.2025.120518","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"410 ","pages":"Article 120518"},"PeriodicalIF":5.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145538796","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":"Exploring the causal biological association between mitochondrial genes and carotid plaques: A multiomics Mendelian randomization study","authors":"Zhuyuan Yu ,&nbsp;Xiangyuan Meng ,&nbsp;Ziyu Zong ,&nbsp;Qi Song ,&nbsp;Yingchao Huo ,&nbsp;Hao Chen","doi":"10.1016/j.atherosclerosis.2025.120570","DOIUrl":"10.1016/j.atherosclerosis.2025.120570","url":null,"abstract":"<div><h3>Background</h3><div>To investigate the causal relationship between mitochondrial genes and the pathogenesis of carotid plaque (CP), a multiomics-integrated Mendelian randomization (MR) analysis was performed in this study.</div></div><div><h3>Methods</h3><div>Leveraging data from the McRae study, UK Biobank, eQTLGen Consortium, and decode database, we extracted mitochondrial gene QTLs at methylation, gene expression, and protein abundance levels as instrumental variables for MR and summary data-based Mendelian randomization (SMR) analyses. Multiomics evidence was classified by integrating MR, SMR, and colocalization results to investigate associations between mitochondria-related genes and CP.</div></div><div><h3>Results</h3><div>Integration of multiomics data across mQTL, eQTL, and pQTL levels revealed 16 genes (<em>GATM, CBR4, PGS1, PTPMT1, SDSL, SLC25A28, SPRYD4, TARS2, ACAT1, GRHPR, METAP1D, NIT2, ACSM2A, AGXT, TOP1MT</em>, and <em>CKMT2</em>) that passed MR and SMR analyses. Among these, <em>GATM</em> demonstrated Tier 1 evidence, showing consistent causal associations with CP across all three levels. Specifically, methylation of cg10760299 in <em>GATM</em> was associated with lower <em>GATM</em> expression, increased protein levels, and a greater risk of CP. However, mtDNA copy number was not significantly associated with CP risk according to MR analysis.</div></div><div><h3>Conclusion</h3><div>This study identifies 16 mitochondrial genes with multiomics evidence linked to CP pathogenesis across genetic, methylation, and protein levels, highlighting the potential role of mitochondrial dysfunction in CP development and the potential of mitochondrial genes as biomarkers and therapeutic targets.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"413 ","pages":"Article 120570"},"PeriodicalIF":5.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997051","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":"ApoB-100: The guardian of LDL stability","authors":"Katariina Öörni ,&nbsp;Lauri Äikäs","doi":"10.1016/j.atherosclerosis.2024.119096","DOIUrl":"10.1016/j.atherosclerosis.2024.119096","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"410 ","pages":"Article 119096"},"PeriodicalIF":5.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290825","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":"Reply to: Residual cardiovascular risk in CKD: Reaffirming the role of remnant cholesterol and inflammation","authors":"Daniel Elías-López ,&nbsp;Camilla Jannie Kobylecki ,&nbsp;Signe Vedel-Krogh ,&nbsp;Takahito Doi ,&nbsp;Børge Grønne Nordestgaard","doi":"10.1016/j.atherosclerosis.2025.120450","DOIUrl":"10.1016/j.atherosclerosis.2025.120450","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"410 ","pages":"Article 120450"},"PeriodicalIF":5.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717284","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":"Fatty liver-index, systemic inflammation and cardiovascular mortality. Results from the LURIC study","authors":"Stephanie Wissel ,&nbsp;Hubert Scharnagl ,&nbsp;Marcus E. Kleber ,&nbsp;Graciela Delgado ,&nbsp;Angela Moissl ,&nbsp;Bernhard Krämer ,&nbsp;Winfried März","doi":"10.1016/j.atherosclerosis.2025.120557","DOIUrl":"10.1016/j.atherosclerosis.2025.120557","url":null,"abstract":"<div><h3>Background and aims</h3><div>The Fatty Liver Index (FLI) has emerged as an indicator of metabolic dysfunction and has been related to cardiovascular outcomes. This study aims to investigate if the association between FLI and cardiovascular mortality is modified by systemic inflammation.</div></div><div><h3>Methods</h3><div>The study population consisted of 3316 participants (mean age 63 years, 30,3 % female) of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. The FLI was calculated using triglycerides, BMI, waist circumference, and gamma-glutamyl transferase (GGT). Systemic inflammatory markers (hsCRP and IL-6) were measured with immunoturbidimetric and ELISA assays. The outcome of interest was cardiovascular mortality. Cox proportional hazard analyses accounting for confounding variables were used for statistical analyses.</div></div><div><h3>Results</h3><div>During a median follow-up of 9.9 years, 603 cardiovascular deaths occurred. Individuals in the highest compared to the lowest FLI tertile were at an increased risk of cardiovascular death (HR 1.39, 95 % CI 1.02–1.89). This association was significantly modified by elevated hsCRP (≥2 mg/L, HR 1.58, 95 % CI 1.10–2.26) and IL-6 (≥3.2 ng/L, (HR 1.93, 95 %CI 1.36–2.74).</div></div><div><h3>Conclusion</h3><div>The Fatty Liver Index is not associated with cardiovascular mortality. However, this relationship is modified by systemic inflammation. These results indicate that liver steatosis is particularly relevant in presence of systemic inflammation which suggests that risk assessment in individuals with steatosis needs to consider both metabolic and inflammatory markers.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"411 ","pages":"Article 120557"},"PeriodicalIF":5.7,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145501939","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":"Sex differences in mortality associated with physical activity before and after acute coronary syndrome","authors":"Sae Young Jae ,&nbsp;Dong-Hyuk Cho ,&nbsp;Setor K. Kunutsor ,&nbsp;Jimi Choi ,&nbsp;Barry A. Franklin ,&nbsp;Jun Gyo Gwon","doi":"10.1016/j.atherosclerosis.2025.120559","DOIUrl":"10.1016/j.atherosclerosis.2025.120559","url":null,"abstract":"<div><h3>Background and aims</h3><div>Sex differences have been suggested in the association between baseline physical activity (PA) and cardiovascular outcomes, with women potentially benefiting more. This study evaluated sex differences in survival benefits of changes in moderate-to-vigorous physical activity (MVPA) before and after acute coronary syndrome (ACS).</div></div><div><h3>Methods</h3><div>We analyzed 30,840 patients with an ACS diagnosis (mean age 60 years; men: 25,069, women: 5771) from the National Health Insurance Service. Changes in MVPA before and after ACS were self-reported and categorized as persistently inactive, MVPA initiation, MVPA cessation, or MVPA continuation. Outcomes included all-cause and cardiovascular disease (CVD) mortality.</div></div><div><h3>Results</h3><div>Over a median follow-up of 5.8 years, 1349 CVD deaths and 4379 all-cause deaths occurred. MVPA initiation was associated with reduced all-cause mortality in men (Hazard Ratio [HR] = 0.77, 95 % Confidence Interval [CI] 0.64–0.93) and women (HR = 0.57, 95 % CI 0.42–0.79). MVPA continuation was associated with reduced all-cause mortality in men and women: (HR = 0.74, 95 % CI 0.63–0.88) and (HR = 0.58, 95 % CI 0.44–0.77). For CVD mortality, MVPA initiation yielded HRs of 0.84 (95 % CI 0.59–1.19) in men and 0.53 (95 % CI 0.31–0.91) in women; MVPA continuation rendered HRs of 0.71 (95 % CI 0.51–0.99) in men and 0.46 (95 % CI 0.29–0.75) in women. Interaction analyses did not suggest significant sex differences in these associations.</div></div><div><h3>Conclusions</h3><div>Initiating or continuing MVPA post-ACS diagnosis is associated with a lower risk of all-cause and CVD mortality, with comparable benefits in men and women; this challenging the notion that women derive greater PA-induced mortality reductions than their male counterparts.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"411 ","pages":"Article 120559"},"PeriodicalIF":5.7,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463693","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":"Nicotine induces m6A-modified eNOS dysregulation to aggravate endothelial injury in male mice","authors":"Guoxia Shi ,&nbsp;Ziquan Jiang ,&nbsp;Zhuo Du ,&nbsp;Sibo Sun ,&nbsp;Dongxu Huang ,&nbsp;Pingping Wan ,&nbsp;Shuang Li ,&nbsp;Manyu Du ,&nbsp;Qiuying Yan ,&nbsp;Bo Yu ,&nbsp;Caiying Tang ,&nbsp;Ping Sun ,&nbsp;Jiannan Dai","doi":"10.1016/j.atherosclerosis.2025.120558","DOIUrl":"10.1016/j.atherosclerosis.2025.120558","url":null,"abstract":"<div><h3>Background and aims</h3><div>Cigarette smoking is a well-established risk factor for vascular injury. However, the effects of nicotine alone remain poorly understood. This study aimed to investigate whether nicotine regulates endothelial nitric oxide synthase (<em>eNOS</em>) expression, thereby contributing to vascular endothelial injury, and to elucidate the critical involvement of N6-Methyladenosine (m6A) modification in this process.</div></div><div><h3>Methods</h3><div>Mice were exposed to 12 weeks of nicotine exposure, to examine its impact on vascular endothelial injury. Human coronary artery endothelial cells were stimulated with nicotine in vitro, and qRT-PCR and MeRIP-qPCR were performed to measure eNOS expression and its m6A modification levels, respectively. RNA pull-down assays were used to identify eNOS mRNA-interacting proteins, and an endothelial-specific methyltransferase-like protein 3 (Mettl3) knockout model and eNOS recombinant adenovirus were utilized to validate the role of eNOS m6A modification in nicotine-induced endothelial injury.</div></div><div><h3>Results</h3><div>Nicotine stimulation induced vascular endothelial injury by activating endothelial cells, thereby increasing their permeability and migration capacity through suppressing <em>eNOS</em> expression. These pathological changes were alleviated in both <em>eNOS</em>-overexpressing and endothelial-specific <em>Mettl3</em> knockout mice. Mechanistically, nicotine increased the m6A modification of <em>eNOS</em> through METTL3. METTL3 then interacted with the YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), which led to mRNA degradation and reduced protein levels via the m6A-dependent pathway.</div></div><div><h3>Conclusions</h3><div>We propose a novel mechanism by which nicotine promotes vascular endothelial injury via METTL3/YTHDF2-mediated m6A modification of <em>eNOS</em> in endothelial cells. This study offers a new insights for the formation of vascular endothelial injury.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"411 ","pages":"Article 120558"},"PeriodicalIF":5.7,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450718","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":"Common genetic variation in the APOE gene and risk of cancer: a systematic review and meta-analysis","authors":"Yousef A. Barakji ,&nbsp;Nanna B. Hupfeld ,&nbsp;Claus A. Bertelsen ,&nbsp;Ruth Frikke-Schmidt ,&nbsp;Sune F. Nielsen ,&nbsp;Katrine L. Rasmussen","doi":"10.1016/j.atherosclerosis.2025.120568","DOIUrl":"10.1016/j.atherosclerosis.2025.120568","url":null,"abstract":"<div><h3>Background and aims</h3><div>Already decades ago, apolipoprotein E (apoE) was suggested to be implemented in risk of cancer. The aim was to investigate the current evidence on the association between <em>APOE</em> ε2/ε3/ε4 carrier status and risk of cancer.</div></div><div><h3>Methods</h3><div>This systematic review and meta-analysis performed per PRISMA guidelines included a search of PubMed and Embase (PROSPERO CRD42024498793). Studies had to report <em>APOE</em> ε2/ε3/ε4 genotype/allele status, and ε33, non-ε4 or non-ε2 served as reference groups.</div></div><div><h3>Results</h3><div>Of 3189 screened records, we included 38 studies in the meta-analysis. For all cancer the risk increased from ε2 to ε3 to ε4 (<em>P</em> for trend: <em>p</em> = 0.01). For breast cancer ε4 was the risk allele (<em>p</em> = 0.03). The risk for colorectal cancer increased from ε2 to ε3 to ε4 (p for trend: <em>p</em> = 0.02). The Odds Ratio (OR) (95 % confidence interval (CI)) for colorectal cancer was 1.07 (1.00–1.13) for ε43 vs. ε33. For lung cancer the OR was 1.52 (1.04–2.2) for ε22 vs. ε33, and 2.80 (1.38–5.69) for ε4 vs. non-ε4. For the analyses for larynx and pharynx cancer, the OR was 0.72 (0.54–0.95) for ε2 vs. non-ε2.</div></div><div><h3>Conclusions</h3><div><em>APOE</em> ε2/ε3/ε4 genotype does not constitute a major risk factor for cancer. Effect sizes were overall small, and we did not find a clear pattern appearing throughout all cancer types with none of the comparisons (for individual alleles/genotypes) statistically significant for risk of all cancer. The study cannot exclude small but biologically interesting allele and genotype specific patterns for some cancer types with ε4 posing to be a risk factor and ε2 a protective factor.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"411 ","pages":"Article 120568"},"PeriodicalIF":5.7,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457431","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":"Loss of ADAM17 in smooth muscle cells enhances their transformation to macrophage-like cells leading to more severe atherosclerosis in mice","authors":"Ilamaran Meganathan ,&nbsp;Tolga Kilic ,&nbsp;Razoan Al Rimon ,&nbsp;Tushar Naiya ,&nbsp;Vidhya Krishnan ,&nbsp;Nikki Atanasova ,&nbsp;Anthony Wong ,&nbsp;Gavin Y. Oudit ,&nbsp;Slava Epelman ,&nbsp;Zamaneh Kassiri","doi":"10.1016/j.atherosclerosis.2025.120567","DOIUrl":"10.1016/j.atherosclerosis.2025.120567","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Atherosclerosis is a multicellular disease, and smooth muscle cells (SMCs) can contribute to plaque formation. ADAM17 (a distintegrin and metalloproteinase-17) is a membrane-bound proteinase that is upregulated in vascular disease and can regulate SMC functions. We investigated the role of ADAM17 in SMCs in atherosclerosis.</div></div><div><h3>Methods &amp; results</h3><div>Human coronary plaques showed a high number of macrophage-like SMCs and ADAM17 expression. Male and female mice with inducible ADAM17 knockdown in SMCs (<em>Ldlr</em>^−/−/<em>Adam17</em>^f/f/<em>Myh11</em>-Cre^ERT2; <em>Ldlr</em>^−/−/<em>Adam17</em>^SMC−KD), ADAM17-intact (<em>Ldlr</em>^−/−/<em>Adam17</em>^f/f; <em>Ldlr</em>^−/−), and genetic control (<em>Ldlr</em>^−/−/<em>Myh11</em>-Cre^ERT2) received Western diet (HCD) or regular chow. <em>Ldlr</em>^−/−/<em>Adam17</em>^SMC−KD-HCD mice developed significantly more plaques, higher aortic cholesterol content, and aortic valve plaque and stiffness compared to <em>Ldlr</em>^−/−-HCD mice, despite a comparable plasma lipid profile. SnRNAseq revealed a marked shift in SMC phenotypes from contractile to macrophage-like forms, and a greater population of proliferating inflammatory macrophages in <em>Ldlr</em>^−/−/<em>Adam17</em>^SMC−KD-HCD compared to <em>Ldlr</em>^−/−-HCD aortas. The plaques in <em>Ldlr</em>^−/−/<em>Adam17</em>^SMC−KD mice showed a higher number of macrophage-like SMCs, decreased expression of SMC proteins (calponin, α-SMA, SM22α) and increased SMC atherogenic marker (galectin-3). <em>In vitro</em>, under atherogenic conditions, <em>Adam17</em>^KD SMCs showed higher lipid content, increased lipid uptake and reduced efflux, associated with increased lipid uptake transporters (CD36, SRA1), and decreased efflux transporter, ABCA1, compared to control SMCs. In <em>Ldlr</em>^−/−/<em>Adam17</em>^SMC−KD-HCD aortas, membrane TNFR1 was stabilized, while the suppressed Ikkß-NFκB-LXRα pathway could underlie the decrease in ABCA1 expression.</div></div><div><h3>Conclusion</h3><div>ADAM17 is a novel regulator of SMC function in atherosclerosis. Its loss increases lipid content in SMCs, transformation into synthetic and macrophage-like states, and worsened atherosclerosis.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"411 ","pages":"Article 120567"},"PeriodicalIF":5.7,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463692","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}