Atherosclerosis最新文献

{"title":"Reply to: “Correspondence on: “Subclinical atherosclerosis: More data – More insights into prevention” ”","authors":"","doi":"10.1016/j.atherosclerosis.2024.118634","DOIUrl":"10.1016/j.atherosclerosis.2024.118634","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593135","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":"Complement factor B, not the membrane attack complex component C9, promotes neointima formation after arterial wire injury","authors":"","doi":"10.1016/j.atherosclerosis.2024.118586","DOIUrl":"10.1016/j.atherosclerosis.2024.118586","url":null,"abstract":"<div><h3>Background and aims</h3><div>Vascular restenosis due to neointima hyperplasia limits the long-term patency of stented arteries, resulting in angioplasty failure. The complement system has been implicated in restenosis. This study aimed to investigate the role of complement factor B (fB), an essential component of the alternative pathway of complement activation, in neointima formation.</div></div><div><h3>Methods</h3><div>Angioplasty wire injury was conducted using 12-week-old mice deficient in fB or C9 (the main component of the membrane attacking complex, C5b-9) and littermate controls and neointima formation were assessed. Vascular smooth muscle cell (SMC) and endothelial cell (EC) proliferation and migration were examined <em>in vitro</em>.</div></div><div><h3>Results</h3><div>fB was mainly detected in SMCs of stenotic arteries from humans and mice. Deletion of fB substantially reduced the neointima area and intima-to-media area ratio without affecting the media area at 28 days after injury. At 7 days after injury, fB deficiency decreased SMC proliferation, unaltering neointimal macrophage infiltration and EC reendothelialization. Vascular SMC-expressed fB, not the circulation-sourced fB, played an essential role in SMC proliferation and migration <em>in vitro</em>. fB deficient mice exhibited lower levels of the soluble form of C5b-9, however, deletion of C9 did not alter neointima formation after wire injury, consistent with the null impact of C9 deficiency on SMC proliferation <em>in vitro</em>.</div></div><div><h3>Conclusions</h3><div>fB promotes neointima formation following wire-induced artery injury independent of forming the membrane-attacking complex. This is attributable to fB-dependent SMC proliferation and migration without affecting EC function. Targeting fB might protect against restenosis after percutaneous coronary intervention.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578097","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":"ERICH4 is not involved in the assembly and secretion of intestinal lipoproteins","authors":"","doi":"10.1016/j.atherosclerosis.2024.118635","DOIUrl":"10.1016/j.atherosclerosis.2024.118635","url":null,"abstract":"<div><h3>Background and aims</h3><div>The small intestine plays a central role in lipid metabolism, most notably the uptake of dietary fats that are packaged into chylomicrons and secreted into the circulation for utilisation by peripheral tissues. While microsomal triglyceride transfer protein (MTP) is known to play a key role in this pathway, the intracellular assembly, trafficking, and secretion of chylomicrons is incompletely understood.</div></div><div><h3>Methods and Results</h3><div>Using human transcriptome datasets to find genes co-regulated with <em>MTTP</em>, we identified <em>ERICH4</em> as a top hit. The gene encodes for glutamate-rich protein 4, a protein of unknown function. REACTOME gene-function prediction tools indicated that ERICH4 is involved in intestinal lipid metabolism. In addition, GWAS data point to a strong relationship between <em>ERICH4</em> and plasma lipids. To validate <em>ERICH4</em> as a lipid gene, we generated whole-body <em>Erich4</em> knockout (<em>Erich4</em>^{<em>−/−</em>}) mice. ERICH4 deficiency<em>,</em> however, did not result in changes in body weight and composition, food intake, circulating plasma lipids, energy absorption and excretion, and tissue weights compared to controls. Additionally, there were no morphological abnormalities seen in the small intestine. Challenging mice with a high-fat diet did not give rise to a phenotype either.</div></div><div><h3>Conclusions</h3><div>Despite prediction tools indicating <em>ERICH4</em> as a strong candidate gene in intestinal lipid metabolism, we here show that ERICH4 does not play a role in intestinal lipid metabolism in mice. It remains to be established whether ERICH4 plays a role in human lipid metabolism.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567536","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":"Publication bias in pharmacogenetics of statin-associated muscle symptoms: A meta-epidemiological study.","authors":"A Gougeon, I Aribi, S Guernouche, J C Lega, J M Wright, C Verstuyft, A Lajoinie, F Gueyffier, G Grenet","doi":"10.1016/j.atherosclerosis.2024.118624","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.118624","url":null,"abstract":"<p><strong>Background and aims: </strong>Statin-associated muscle symptoms (SAMS) are a major cause of treatment discontinuation. Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend dose adjustment for statin treatment according to known SLCO1B1 genotype to reduce SAMS. We hypothesized that the association between SLCO1B1 genotype and SAMS is misestimated because of publication bias.</p><p><strong>Methods: </strong>We searched published systematic reviews on the association between SLCO1B1 genotype and SAMS. To assessed publication bias, we used funnel plot visual inspection, Egger's test, and the Bayes Factor (BF_{Publication-bias}) from Robust Bayesian Meta-Analysis (RoBMA). We compared the odds ratios (OR_Uncorrected) from meta-analyses before and after correcting for publication bias using trim-and-fill (OR_Trim&Fill) and RoBMA (OR_RoBMA) methods.</p><p><strong>Results: </strong>We included 8 cohort and 11 case-control studies, totaling 62 OR of three SLCO1B1 genotypes and six statin drugs. In the primary analysis, the funnel plot was suggestive of publication bias, confirmed by Egger's test (p=0.001) and RoBMA (BF_{Publication-bias} = 18). Correcting the estimate for publication bias resulted in loss of the association, from a significant OR_Uncorrected (1.31 95%CI [1.13-1.53]) to corrected ORs suggesting no difference: OR_Trim&Fill (1.07 95%CI [0.89-1.30]) and OR_RoBMA (1.02 95%CI [1.00-1.33]). This suggested that publication bias overestimated the association by 18 % and 23 %, respectively. Similar results were found for genotype rs4149056, simvastatin and atorvastatin.</p><p><strong>Conclusions: </strong>The effect of the SLCO1B1 genotype on the risk of developing SAMS is overestimated in the published literature, especially rs4149056. This could lead prescribers to incorrectly decreasing statin doses or even avoiding statin use, leading to a loss of the potential cardiovascular benefit of statins.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563490","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":"Unraveling the complex interplay of PPARα and age in cardiac metabolism: Implications for managing age-related cardiac dysfunctions.","authors":"Sina Rashedi, Mohammad Keykhaei","doi":"10.1016/j.atherosclerosis.2024.118627","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.118627","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493740","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":"Single bolus PCSK9 Inhibition: A new approach to plaque stabilisation.","authors":"Stephen J Nicholls, Gavin Pr Manmathan","doi":"10.1016/j.atherosclerosis.2024.118628","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.118628","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493739","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":"Comparison of pooled cohort equation and PREVENT™ risk calculator for statin treatment allocation","authors":"","doi":"10.1016/j.atherosclerosis.2024.118626","DOIUrl":"10.1016/j.atherosclerosis.2024.118626","url":null,"abstract":"<div><h3>Background and aims</h3><div>Effective hypercholesterolemia management is linked to lower all-cause and cardiovascular mortality. The 2018 AHA/ACC guidelines recommended using the Pooled Cohort Equations (PCE) for lipid management, but these may overestimate risk and be less accurate for certain racial groups. The AHA's new PREVENT equation, which omits race and includes cardiometabolic factors, aims to provide a more accurate risk assessment for a diverse population. However, it has not yet been applied to a nationally representative US population, and implementation guidelines are still lacking. Our study aimed to evaluate potential changes in hypercholesterolemia management for primary prevention by using the PREVENT equation instead of the PCE.</div></div><div><h3>Methods</h3><div>Analyzing pre-pandemic NHANES 2017–2020 data, participants aged 40–75 without prior lipid-lowering treatment or other compelling indication were identified for elevated risk (≥7.5 %) using the PCE and PREVENT equations. We assessed risk shifts and indications for statin therapy, comparing the two risk equations. NHANES guidelines with weighting were followed to obtain US nationally representative estimates.</div></div><div><h3>Results</h3><div>Out of 77, 647, 807 (unweighted = 2494) participants, 81.0 % had no change in risk. The PCE flagged 18.8 % (n = 14,614,094) of participants at elevated risk not identified by PREVENT, while 0.20 % (n = 107,813) were flagged only by PREVENT. Participants identified solely by the PCE were older, with higher systolic blood pressure and increased estimated glomerular filtration rates.</div><div>Indications for statin therapy were largely unchanged (81.0 %). PREVENT newly identified (0.20 %) for moderate-intensity therapy and none for high-intensity therapy. Participants qualifying for moderate intensity therapy by the PCE were reclassified to no therapy in 74.59 % of cases, while 25.41 % remained unchanged. Participants qualifying for high-intensity therapy by the PCE were reclassified to moderate therapy in 93.97 % of cases, and 6.03 % were reclassified to no therapy.</div></div><div><h3>Conclusions</h3><div>The PREVENT equation notably differs in identifying hypercholesterolemia candidates compared to the PCE. Its adoption would influence cardiovascular risk reduction therapy recommendations, emphasizing the need for comprehensive studies to understand its long-term impact and reevaluate the threshold of treatment strategies for improved patient outcomes.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493741","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":"Statin use is associated with less ST-elevation versus non-ST-elevation myocardial infarction in a nationwide study","authors":"","doi":"10.1016/j.atherosclerosis.2024.118625","DOIUrl":"10.1016/j.atherosclerosis.2024.118625","url":null,"abstract":"<div><h3>Background and aims</h3><div>Statin therapy reduces myocardial infarction rate but whether it is associated with a shift of ST-elevation myocardial infarction (STEMI) towards non-ST-elevation myocardial infarction (non-STEMI) remains unknown. Thus, we tested the hypothesis that statin use is associated with less STEMI relative to non-STEMI in first-time myocardial infarction.</div></div><div><h3>Methods</h3><div>In a nationwide study, including 66,896 patients with first-time myocardial infarction between 2010 and 2021, we obtained multivariable risk estimates for STEMI <em>versus</em> non-STEMI according to any statin use, cumulated statin use, and daily statin dose. Furthermore, we obtained hazard ratios for 60-day mortality (5545 deaths) following myocardial infarction according to type of infarction.</div></div><div><h3>Results</h3><div>Odds ratios for STEMI <em>versus</em> non-STEMI were 0.81 (95 % CI:0.77–0.85) and 1.07 (1.01–1.13) in current and previous statin users compared to never statin users. Cumulated statin exposure yielded odds ratios of 0.96 (0.87–1.07) for &lt;2 statin-years, 0.87 (0.79–0.95) for 2–4.9 statin-years, 0.80 (0.74–0.87) for 5–10 statin-years, and 0.75 (0.70–0.80) for &gt;10 statin-years compared to never users. Corresponding odds ratios for statin dose intensity were 0.89 (0.84–0.95) for low-intensity, 0.77 (0.73–0.82) for moderate-intensity, and 0.70 (0.63–0.77) for high-intensity. Results were similar in multiple sensitivity analyses and using a cohort design. The hazard ratio for 60-day mortality after first-time STEMI <em>versus</em> non-STEMI was 2.24 (2.13–2.37).</div></div><div><h3>Conclusions</h3><div>In this nationwide study, prior statin use is associated with less STEMI relative to non-STEMI in a dose dependent manner. This indicates that statin therapy, in addition to reducing myocardial infarction event rates, also result in a less severe presentation of myocardial infarctions.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493742","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":"Shear stress is uncoupled from atheroprotective KLK10 in atherosclerotic plaques","authors":"","doi":"10.1016/j.atherosclerosis.2024.118622","DOIUrl":"10.1016/j.atherosclerosis.2024.118622","url":null,"abstract":"<div><h3>Background and aims</h3><div>Physiological shear stress promotes vascular homeostasis by inducing protective molecules in endothelial cells (EC). However, physiological shear stress has been linked to atherosclerosis progression in some individuals with heightened cardiovascular risk. To address this apparent paradox, we hypothesized that diseased arteries may exhibit reduced responsiveness to the protective effects of physiological shear stress. Consequently, we compared the transcriptome of EC exposed to physiological shear stress in healthy arteries <em>versus</em> atherosclerotic conditions.</div></div><div><h3>Methods</h3><div>Employing 3D light sheet imaging and computational fluid dynamics, we identified NOS3 as a marker of physiological shear stress in both healthy and atherosclerotic murine arteries. Single-cell RNA sequencing was performed on EC from healthy (C57BL/6) mice, mildly diseased (<em>Apoe</em>^{<em>−/−</em>} normal diet) mice, and highly diseased (<em>Apoe</em>^{<em>−/−</em>} high fat diet) mice. The transcriptomes of <em>Nos3</em>^high cells (exposed to physiological shear stress) were compared among the groups.</div></div><div><h3>Results</h3><div><em>Nos3</em>^high EC were associated with several markers of physiological shear stress in healthy arteries. Clustering of <em>Nos3</em>^high EC revealed 8 different EC subsets that varied in proportion between healthy and diseased arteries. Cluster-specific nested functional enrichment of gene ontology terms revealed that <em>Nos3</em>^high EC in diseased arteries were enriched for inflammatory and apoptotic gene expression. These alterations were accompanied by changes in several mechanoreceptors, including the atheroprotective factor KLK10, which was enriched in <em>Nos3</em>^high EC in healthy arteries but markedly reduced in severely diseased arteries.</div></div><div><h3>Conclusions</h3><div>Physiological shear stress is uncoupled from atheroprotective KLK10 within atherosclerotic plaques. This sheds light on the complex interplay between shear stress, endothelial function, and the progression of atherosclerosis in individuals at risk of cardiovascular complications.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441174","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":"Role of fatty acids in the pathogenesis of ß-cell failure and Type-2 diabetes.","authors":"Cecilia Jiménez-Sánchez, Lucie Oberhauser, Pierre Maechler","doi":"10.1016/j.atherosclerosis.2024.118623","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.118623","url":null,"abstract":"<p><p>Pancreatic ß-cells are glucose sensors in charge of regulated insulin delivery to the organism, achieving glucose homeostasis and overall energy storage. The latter function promotes obesity when nutrient intake chronically exceeds daily expenditure. In case of ß-cell failure, such weight gain may pave the way for the development of Type-2 diabetes. However, the causal link between excessive body fat mass and potential degradation of ß-cells remains largely unknown and debated. Over the last decades, intensive research has been conducted on the role of lipids in the pathogenesis of ß-cells, also referred to as lipotoxicity. Among various lipid species, the usual suspects are essentially the non-esterified fatty acids (NEFA), in particular the saturated ones such as palmitate. This review describes the fundamentals and the latest advances of research on the role of fatty acids in ß-cells. This includes intracellular pathways and receptor-mediated signaling, both participating in regulated glucose-stimulated insulin secretion as well as being implicated in ß-cell dysfunction. The discussion extends to the contribution of high glucose exposure, or glucotoxicity, to ß-cell defects. Combining glucotoxicity and lipotoxicity results in the synergistic and more deleterious glucolipotoxicity effect. In recent years, alternative roles for intracellular lipids have been uncovered, pointing to a protective function in case of nutrient overload. This requires dynamic storage of NEFA as neutral lipid droplets within the ß-cell, along with active glycerolipid/NEFA cycle allowing subsequent recruitment of lipid species supporting glucose-stimulated insulin secretion. Overall, the latest studies have revealed the two faces of the same coin.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399151","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}