Atherosclerosis最新文献

{"title":"Special issue: Decoding atherosclerosis: Epigenetics and functional genomics.","authors":"Casey E Romanoski, Minna U Kaikkonen","doi":"10.1016/j.atherosclerosis.2025.119230","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2025.119230","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119230"},"PeriodicalIF":4.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109492","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":"Effectiveness of long-term weight reduction following bariatric surgery on cardiovascular risk.","authors":"Shin-Ichiro Miura","doi":"10.1016/j.atherosclerosis.2025.119245","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2025.119245","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119245"},"PeriodicalIF":4.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126209","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":"Association of Lipoprotein(a) with cardiovascular events among individuals with autoimmune conditions","authors":"Pamela L. Alebna ,&nbsp;Mathew Ambrosio ,&nbsp;Maxwell Martin ,&nbsp;Sarah Martey ,&nbsp;Jared A. Spitz ,&nbsp;Garima Sharma ,&nbsp;Benjamin Van Tassell ,&nbsp;Dave L. Dixon ,&nbsp;W. Gregory Hundley ,&nbsp;Fadi N. Salloum ,&nbsp;Anurag Mehta","doi":"10.1016/j.atherosclerosis.2025.119244","DOIUrl":"10.1016/j.atherosclerosis.2025.119244","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune conditions are associated with systemic inflammation, which elevates the risk of major adverse cardiovascular events (MACE). Systemic inflammation can increase plasma lipoprotein(a) [Lp(a)] levels by activating the interleukin-6 response element within the <em>LPA</em> gene promoter region. However, the association between elevated plasma Lp(a) and MACE risk in individuals with autoimmune conditions remains unclear.</div></div><div><h3>Methods</h3><div>We analyzed data from 353,035 UK Biobank participants without cardiovascular disease, including 11,229 individuals with autoimmune conditions such as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, and others. Cox proportional hazards regression models and Kaplan-Meier survival curves assessed the association between elevated Lp(a) (≥125 nmol/L), autoimmune status, and time to MACE (myocardial infarction, stroke, cardiovascular death).</div></div><div><h3>Results</h3><div>Over a median follow-up of 14 years, 19,091 MACEs occurred. Autoimmune conditions (HR, 1.30; 95 % CI, 1.20–1.41; P &lt; 0.001) and elevated Lp(a) (HR, 1.24; 95 % CI, 1.18–1.30; P &lt; 0.001) were independently associated with increased MACE risk. The interaction between autoimmune conditions and elevated Lp(a) was not significant (p = 0.40). Compared to participants with neither risk factor, those with both autoimmune conditions and elevated Lp(a) had the highest MACE risk (HR, 1.77; 95 % CI, 1.46–2.15; P &lt; 0.001). Elevated MACE risk was also observed in individuals with only elevated Lp(a) (HR, 1.23; 95 % CI, 1.17–1.29; P &lt; 0.001) or only autoimmune conditions (HR, 1.28; 95 % CI, 1.18–1.40; P &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Autoimmune disease status and elevated Lp(a) level have an independent and additive joint association with MACE risk. This may have implications for Lp(a) lowering therapy use in high-risk primary prevention populations.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"406 ","pages":"Article 119244"},"PeriodicalIF":4.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090503","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":"Experimental evidence on colchicine's mode of action in human carotid artery plaques","authors":"Alexander von Ehr ,&nbsp;Ines Derya Steenbuck ,&nbsp;Charlotte Häfele ,&nbsp;Felix Remmersmann ,&nbsp;Tamara A. Vico ,&nbsp;Carolin Ehlert ,&nbsp;Diana Lindner ,&nbsp;Dennis Wolf ,&nbsp;Stefan Tholen ,&nbsp;Oliver Schilling ,&nbsp;Martin Czerny ,&nbsp;Dirk Westermann ,&nbsp;Ingo Hilgendorf","doi":"10.1016/j.atherosclerosis.2025.119239","DOIUrl":"10.1016/j.atherosclerosis.2025.119239","url":null,"abstract":"<div><h3>Background and aims</h3><div>Atherosclerosis, driven by inflammation, is a leading cause of cardiovascular events. Recent clinical trials have highlighted the therapeutic potential of anti-inflammatory treatments. Consequently, colchicine is being recommended for secondary prevention in current guidelines, although the drug's mechanistic actions are not fully understood.</div></div><div><h3>Methods</h3><div>To this end, we conducted a multiomic investigation of colchicine's effect on human carotid plaques. Sections from endarterectomy specimens were exposed to colchicine at concentrations of 2 ng/ml and 10 ng/ml <em>ex vivo</em> for 24 h and compared to untreated segments of the same plaque. Gene expression changes were analyzed by bulk RNA sequencing, and plaque secretomes underwent mass spectrometry for proteomic analysis. <em>In situ</em> cell proliferation was assessed by histology.</div></div><div><h3>Results</h3><div>Our data indicate, that colchicine suppresses neutrophil and platelet degranulation and activation, collagen degradation and atheromatous plaque macrophage proliferation in a dose-dependent manner in human plaques, while stimulating myofibroblast activation. Unexpectedly, interleukine (IL)-1beta release from colchicine treated plaques was not reduced. These results indicate that the inflammasome may not be the predominant target of low-dose colchicine in human carotid artery plaques.</div></div><div><h3>Conclusion</h3><div>Our study identifies multifactorial pathways through which colchicine, the first cardiovascular guideline-recommended anti-inflammatory drug, predominantly acts on human atherosclerotic lesions beyond the inflammasome. Targeting neutrophil and platelet degranulation, collagen degradation and macrophage proliferation, selectively, may provide substantial therapeutic benefit in atherosclerotic cardiovascular disease without colchicine's undesired side effects.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"406 ","pages":"Article 119239"},"PeriodicalIF":4.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068514","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":"Low and high air temperature and cardiovascular risk.","authors":"Wenli Ni, Ashtyn T Areal, Katharina Lechner, Susanne Breitner, Siqi Zhang, Margarethe Woeckel, S Claire Slesinski, Nikolaos Nikolaou, Marco Dallavalle, Tamara Schikowski, Alexandra Schneider","doi":"10.1016/j.atherosclerosis.2025.119238","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2025.119238","url":null,"abstract":"<p><p>Temperature extremes are one facet of global warming caused by climate change. They have a broad impact on population health globally. Due to specific individual- and area-level factors, some subgroups of the population are at particular risk. Observational data has demonstrated that the association between temperature and mortality and cardiovascular mortality is U- or J-shaped. This means that beyond an optimal temperature, both low and high temperatures increase cardiovascular risk. In addition, there is emerging epidemiological data showing that climate change-related temperature fluctuations may be particularly challenging for cardiovascular health. Biological plausibility for these observations comes from the effect of cold, heat, and temperature fluctuations on risk factors for cardiovascular disease. Shared mechanisms of heat and cold adaptation include sympathetic activation, changes in vascular tone, increased cardiac strain, and inflammatory and prothrombotic stimuli. The confluence of these mechanisms can result in demand ischemia and/or atherosclerotic plaque rupture. In conclusion, public health and individual-level measures should be taken to protect susceptible populations, such as patients with risk factors and/or pre-existing cardiovascular disease, from the adverse effects of non-optimal temperatures. This review aims to provide an overview of the association between temperature extremes and cardiovascular disease through the lens of pathophysiology and observational data. It also highlights some specific meteorological aspects, gives insight to the interplay of air temperature and air pollution, touches upon social dimensions of climate change, and tries to give a brief outlook into what to expect from the future.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119238"},"PeriodicalIF":4.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092692","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":"Association of low-grade inflammation and elevated remnant cholesterol with risk of ASCVD and mortality in impaired renal function","authors":"Daniel Elías-López ,&nbsp;Camilla Jannie Kobylecki ,&nbsp;Signe Vedel-Krogh ,&nbsp;Takahito Doi ,&nbsp;Børge Grønne Nordestgaard","doi":"10.1016/j.atherosclerosis.2025.119241","DOIUrl":"10.1016/j.atherosclerosis.2025.119241","url":null,"abstract":"<div><h3>Background and aims</h3><div>Low-grade inflammation and elevated remnant cholesterol are associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality. We hypothesized that each confers risk of myocardial infarction, ASCVD, and all-cause mortality in individuals with impaired renal function.</div></div><div><h3>Methods</h3><div>We included 102 906 individuals from the Copenhagen General Population Study, of which 9 935 had impaired renal function with estimated glomerular filtration rate &lt;60 mL/min/1.73 m2. Remnant cholesterol was calculated from a standard lipid profile. ASCVD was myocardial infarction, coronary heart disease death, ischemic stroke, or coronary revascularization.</div></div><div><h3>Results</h3><div>In individuals with impaired renal function, we observed 566 myocardial infarctions, 1 122 ASCVD events, and 3 139 deaths. Compared to individuals with low C-reactive protein and remnant cholesterol, multivariable adjusted hazard ratios for myocardial infarction were 1.12 (95 % confidence intervals: 0.86–1.46) in individuals with low C-reactive protein and high remnant cholesterol, 1.28 (1.00–1.65) in individuals with high C-reactive protein and low remnant cholesterol, and 1.39 (1.10–1.76) in individuals with both high C-reactive protein and remnant cholesterol. Corresponding hazard ratios for ASCVD were 1.07 (0.89–1.28), 1.09 (0.91–1.30), and 1.33 (1.13–1.57); and for all-cause mortality 0.96 (0.85–1.07), 1.18 (1.07–1.30), and 1.20 (1.09–1.33), respectively.</div></div><div><h3>Conclusions</h3><div>In individuals with impaired renal function, low-grade inflammation and elevated remnant cholesterol jointly conferred the highest risk of myocardial infarction, ASCVD, and all-cause mortality.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"406 ","pages":"Article 119241"},"PeriodicalIF":4.9,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138477","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":"Minigene splicing reporter assay: a high-stake tool for genetic diagnosis in familial hypobetalipoproteinemia","authors":"Zoé Henry ,&nbsp;Alexandre Janin ,&nbsp;Séverine Nony ,&nbsp;Oriane Marmontel ,&nbsp;Sybil Charrière ,&nbsp;Philippe Moulin ,&nbsp;Marie Marrec ,&nbsp;Matthieu Wargny ,&nbsp;Bertrand Cariou ,&nbsp;Mathilde Di Filippo","doi":"10.1016/j.atherosclerosis.2025.119236","DOIUrl":"10.1016/j.atherosclerosis.2025.119236","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Familial hypobetalipoproteinemia 1 (FHBL-SD2) is the most common monogenic form of primary hypocholesterolaemia, related to truncating variants in the <em>APOB</em> gene encoding apolipoprotein B. Due to its high level of complexity, variants of uncertain significance (VUS) require further investigations. This study aims to demonstrate the value of setting minigene assays in the FHBL-SD2's genetic diagnosis.</div></div><div><h3>Methods</h3><div>Four <em>APOB</em> VUS occurring in patients with a FHBL-SD2 phenotype were considered. <em>In silico</em> analysis were performed with six software programs supposed to predict the potential splicing effect. Then, functional consequences were studied <em>in vitro</em> using a minigene splicing reporter assay.</div></div><div><h3>Results</h3><div>An effect on splicing was predicted <em>in silico</em> for the 4 variants, with the activation of a cryptic acceptor site for c.694-13A&gt;G and c.1471-6A&gt;G variants, and the use of a cryptic donor site for c.1123A&gt;G and c.1470G&gt;A variants. Minigene study showed a complete effect on splicing for 3 mutations, confirming the <em>in silico</em> predictions. All of these transcripts result in premature truncated variants. Therefore, these variants were reclassified as likely pathogenic and causative of FHBL-SD2. However, no effect was shown either in HeLA and HuH7 cells for the c.1470G&gt;A variant.</div></div><div><h3>Conclusions</h3><div>Minigene study appears to be a promising and valuable tool to enhance the diagnostic accuracy of FHBL-SD2. It emphasizes the challenge in interpreting VUS and underscores the importance of establishing a clear strategy to assess their significance. Therefore, promoting minigene studies would be beneficial to understand precisely the impact of splicing variants.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"405 ","pages":"Article 119236"},"PeriodicalIF":4.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935928","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":"Atheroprotective roles of exercise-regulated microRNAs","authors":"Shuo Ke ,&nbsp;Xiaoqin Cao ,&nbsp;Xiaohui Lu ,&nbsp;Jinhong Xu ,&nbsp;Chen-Yu Zhang ,&nbsp;Li Xu ,&nbsp;Xiaohong Jiang","doi":"10.1016/j.atherosclerosis.2025.119229","DOIUrl":"10.1016/j.atherosclerosis.2025.119229","url":null,"abstract":"<div><div>Cardiovascular disease remains the leading cause of death worldwide, with atherosclerosis (AS) serving as a critical underlying pathological process and major risk factor. Regular physical exercise is widely recognized as an effective strategy to reduce the risks and severity of AS, yet the precise molecular mechanisms through which exercise exerts its protective effects are still not fully understood. MicroRNAs (miRNAs), key regulators of gene expression, play integral roles in the progression of AS by influencing vascular function, lipid metabolism, and inflammation. The exercise-induced improvement of AS is a complex process, with miRNAs playing essential roles not only within cells and tissues but also circulating stably in the bloodstream as novel signaling molecules. These circulating miRNAs mediate communication between organs and tissues, acting as potential biomarkers that could provide deeper, systemic insights into the metabolic benefits of exercise. In this review, we explore recent advancements in our understanding of how exercise affects both intracellular and circulating miRNAs. We emphasize how exercise-regulated miRNAs contribute to endothelial function, promote lipid metabolism across various metabolic organs, and reduce monocyte-mediated systemic inflammation, while also addressing their role in alleviating frailty. Circulating miRNAs, which dynamically reflect tissue-specific responses to exercise, hold great promise as diagnostic and prognostic biomarkers for AS. Moreover, we discuss the challenges and future directions in this field, aiming to uncover how exercise-induced miRNA modulation could offer innovative therapeutic strategies for the prevention and treatment of AS.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"405 ","pages":"Article 119229"},"PeriodicalIF":4.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935926","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":"Coronary spotty calcification, compared with macro calcification, is associated with a higher level of vascular inflammation and plaque vulnerability in patients with stable angina","authors":"Daichi Fujimoto ,&nbsp;Daisuke Kinoshita ,&nbsp;Keishi Suzuki ,&nbsp;Takayuki Niida ,&nbsp;Haruhito Yuki ,&nbsp;Iris McNulty ,&nbsp;Hang Lee ,&nbsp;Hiromasa Otake ,&nbsp;Junya Shite ,&nbsp;Maros Ferencik ,&nbsp;Damini Dey ,&nbsp;Fernando Alfonso ,&nbsp;Tsunekazu Kakuta ,&nbsp;Ik-Kyung Jang","doi":"10.1016/j.atherosclerosis.2025.119237","DOIUrl":"10.1016/j.atherosclerosis.2025.119237","url":null,"abstract":"<div><h3>Background and aims</h3><div>Spotty calcification in the coronary arteries is considered to represent plaque vulnerability, whereas more advanced calcification is thought to be a feature of advanced stable plaque. However, data supporting this notion is limited. Inflammation plays a key role in atherogenesis, including the formation of early-stage calcification. We aimed to correlate spotty calcification assessed by optical coherence tomography (OCT) with vascular inflammation assessed by percutaneous coronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CCTA) and OCT-derived plaque vulnerability.</div></div><div><h3>Methods</h3><div>Patients with stable angina pectoris who had both CCTA and OCT prior to coronary intervention were included. Patients were classified into two groups according to the type of calcification assessed by OCT at the target lesion: spotty calcification (maximal calcification arc &lt;90° and length &lt;4 mm) and advanced calcification (maximal calcification arc ≥90° or length ≥4 mm) group. Non-calcified plaques, and plaques with mixed spotty and advanced calcification were excluded.</div></div><div><h3>Results</h3><div>Among 355 patients, 77 had spotty calcifications and 72 had advanced calcification. The spotty calcification group showed a significantly higher level of PCAT attenuation of target vessel (−69.6 [-75.2 to −66.1] vs. −74.6 [-83.1 to −69.7 HU], <em>p</em> &lt; 0.001) and a significantly higher prevalence of lipid-rich plaque (94.8 % vs. 72.2 %, <em>p</em> &lt; 0.001) and macrophage (77.9 % vs. 59.7 %, <em>p</em> = 0.016), compared with the advanced calcification group.</div></div><div><h3>Conclusions</h3><div>Plaques with spotty calcification are associated with a higher level of perivascular inflammation and a higher prevalence of features of plaque vulnerability than those with advanced calcification.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"405 ","pages":"Article 119237"},"PeriodicalIF":4.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935929","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":"Accelerated atherosclerosis associated with immune checkpoint inhibitors: a systematic review and meta-analysis of pre-clinical studies","authors":"Anniek Strijdhorst ,&nbsp;Winnie G. Vos ,&nbsp;Laura A. Bosmans ,&nbsp;Kim E. Dzobo ,&nbsp;Pascal J.H. Kusters ,&nbsp;Nordin M.J. Hanssen ,&nbsp;Jeffrey Kroon ,&nbsp;Esther Lutgens ,&nbsp;Hanneke W.M. van Laarhoven ,&nbsp;Tom T.P. Seijkens ,&nbsp;Nick van Es","doi":"10.1016/j.atherosclerosis.2025.119219","DOIUrl":"10.1016/j.atherosclerosis.2025.119219","url":null,"abstract":"<div><h3>Background</h3><div>Patients with cancer treated with immune checkpoint inhibitors are at increased risk of myocardial infarction and ischemic stroke. The mechanism is incompletely understood but may involve accelerated atherosclerosis due to enhanced inflammation. Pre-clinical studies may provide insight in these mechanisms.</div></div><div><h3>Aim</h3><div>To assess the effects of modulating co-inhibitory immune checkpoint proteins on atherosclerosis progression in animal models.</div></div><div><h3>Methods</h3><div>A systematic review was performed in MEDLINE, Embase, Web of Science, and Scopus up to March 2025. Animal studies were included if the effect of modulation of programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and/or lymphocyte-activation gene 3 (LAG-3) on atherosclerotic plaque size was evaluated. Secondary outcomes were plaque composition and systemic inflammation. The ratios of means (RoM) across the studies were pooled in a random effects meta-analysis. Risk of bias was assessed using the SYRCLE tool, focusing on randomization, blinding, and completeness of outcome reporting.</div></div><div><h3>Results</h3><div>Fourteen eligible studies were included. All studies used an atherosclerotic mouse model (ApoE^−/−, Ldlr^−/−, ApoE3∗Leiden, or AAV8-PCSK9) and either evaluated pharmacological or genetic modulation of co-inhibitory immune checkpoint proteins. Upon inhibition, atherosclerotic plaque size in the aorta was 53 % higher in exposed mice compared to control mice (RoM, 1.53; 95 % CI, 1.29–1.83; <em>I</em>² = 89 %). Plaque composition was predominantly characterized by a greater abundance of CD4⁺ T cells, CD8⁺ T cells, and macrophages. Studies stimulating co-inhibitory immune checkpoint proteins corroborated these findings and demonstrated that atherosclerotic plaque size was reduced by 28 % in treated mice compared to controls (RoM, 0.72; 95 % CI, 0.65–0.80; I2 = 85 %). This reduction was paralleled by a decrease in the number of macrophages and T cells in plaques.</div></div><div><h3>Conclusion</h3><div>Immune checkpoint inhibition leads to increased plaque inflammation and a significant increase in murine atherosclerotic plaque size. These changes may reflect the cause of the increased risk of myocardial infarction and ischemic stroke in patients treated with immune checkpoint inhibitors.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"405 ","pages":"Article 119219"},"PeriodicalIF":4.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935927","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}