Atherosclerosis plus最新文献

{"title":"Bisphosphonates use is associated with increased coronary artery calcification in the general population: The Rotterdam study","authors":"Mitra Nekouei Shahraki ,&nbsp;Layal Chaker ,&nbsp;Evert van Velsen ,&nbsp;Mare van Overbruggen ,&nbsp;Chris Heugens ,&nbsp;Maryam Kavousi ,&nbsp;Bruno H. Stricker ,&nbsp;Daniel Bos","doi":"10.1016/j.athplu.2026.01.001","DOIUrl":"10.1016/j.athplu.2026.01.001","url":null,"abstract":"<div><h3>Aims</h3><div>Bisphosphonates may influence arterial calcification through mechanisms shared with bone formation. As treatment often extends over several years, assessing the arterial effects requires long-term follow-up. This population-based cohort estimated the long-term association of bisphosphonates with calcification across multiple key arterial sites.</div></div><div><h3>Methods</h3><div>We included 2399 Rotterdam Study participants with baseline CT-assessed calcification in the coronary arteries (CAC), aortic arch (AAC), and extra/intracranial carotid arteries (ECAC and ICAC). Among these, 815 participants underwent repeat CT after a mean of 13.6 years. Pharmacy-linked data provided cumulative information on bisphosphonate use from study entry to follow-up. Multivariable linear and mixed-effects regressions evaluated associations between bisphosphonate use, duration, and the dose-response of duration with calcification volume.</div></div><div><h3>Results</h3><div>Long-term bisphosphonate use (&gt;5 years) was statistically significantly associated with larger baseline CAC compared with both never use (β [95 % CI]: 0.42 [0.10, 0.73]) and short-term use (<em>p-interaction</em> = 0.02). At follow-up, prolonged use (mean duration: 4.9 years) was also significantly associated with increased CAC. Effect estimates increased across quartiles of duration for CAC, AAC, and ECAC (but not ICAC), with a significant linear trend only for CAC (<em>p-trend</em> &lt; 0.0001), suggesting a dose-response relationship. Across arterial sites, CAC showed the largest effect estimates, ICAC the smallest.</div></div><div><h3>Conclusions</h3><div>Long-term bisphosphonate use is associated with increased arterial calcification, most notably with increased CAC, with a dose-response relationship further strengthening this observation. Large-scale observational studies are encouraged to use advanced causal inference methods to evaluate this long-term association and provide additional evidence to strengthen the causal interpretation.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Pages 19-27"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role and mechanism of G9A-BMP2 in calcification-induced formation of unstable plaque","authors":"Wenjuan Yang ,&nbsp;Zheng Ma ,&nbsp;Ying Cui ,&nbsp;Shaobin Jia","doi":"10.1016/j.athplu.2026.02.002","DOIUrl":"10.1016/j.athplu.2026.02.002","url":null,"abstract":"<div><h3>Background</h3><div>G9A, a histone methyltransferase that facilitates H3K9 dimethylation, has been implicated in the epigenetic regulation of vascular processes. This study encapsulates its involvement in the calcification and stability of atherosclerotic plaques, further investigating its interaction with bone morphogenetic protein 2 (BMP2), a pivotal factor in vascular calcification, unveiling that G9A fosters plaque calcification and instability via the BMP2 signaling pathway.</div></div><div><h3>Methods</h3><div>The progression of unstable plaques, histone methylation status, and vascular calcification incidence were monitored in the carotid plaques of ApoE^−/− mice subjected to a high-fat diet over 30 weeks. Additionally, these parameters were scrutinized in pathological specimens from patients who underwent carotid plaque excision. In vitro, rat thoracic aortic smooth muscle A7R5 cells were cultured, with the G9A gene being manipulated through techniques of gene knockdown and overexpression.</div></div><div><h3>Results</h3><div>In ApoE^−/−mice and human carotid arteries, calcification exacerbated plaque instability in the context of a high-fat diet. This phenomenon was accompanied by elevated levels of G9A and dimethylation of histone H3 at lysine 9, alongside G9A expression in vitro. The absence of G9A in vitro impeded the calcification process of vascular smooth muscle cells (VSMCs), whereas G9A overexpression prompted a shift in the phenotypic attributes of smooth muscle cells.</div></div><div><h3>Conclusions</h3><div>Our findings indicate that G9A amplifies vascular calcification through the activation of Bmp2 signaling, a fundamental mediator of vascular calcification. The relationship between vascular calcification and the emergence of unstable plaques may be intricately associated with histone methylation.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Pages 77-87"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterozygous transferrin receptor 1 deletion reduces atherosclerotic lesion formation in apolipoprotein E-deficient mice","authors":"Yoshiro Naito,&nbsp;Tetsuo Horimatsu,&nbsp;Masanori Asakura,&nbsp;Masaharu Ishihara","doi":"10.1016/j.athplu.2025.12.003","DOIUrl":"10.1016/j.athplu.2025.12.003","url":null,"abstract":"<div><h3>Background</h3><div>Transferrin receptor 1 (TfR1), an intracellular iron receptor, has multiple biological functions. We have previously reported that aortic TfR1 expression increases in human and murine abdominal aortic aneurysm, but its role in the development of atherosclerosis remains unclear. In the present study, we generated apolipoprotein-E (ApoE) and TfR1 deficient mice and examined the impact of its deletion on the development of atherosclerosis.</div></div><div><h3>Methods and results</h3><div>Homozygous ApoE deficient (<em>ApoE</em>^{<em>−/−</em>}) mice were crossbred to heterozygous TfR1 deficient (<em>TfR1</em>^{<em>+/−</em>}) mice to generate ApoE and TfR1 deficient (<em>ApoE</em>^{<em>−/−</em>}<em>/TfR1</em>^{<em>+/−</em>}) mice. <em>ApoE</em>^{<em>−/−</em>} and <em>ApoE</em>^{<em>−/−</em>}<em>/TfR1</em>^{<em>+/−</em>} mice presented a similar phenotype including body weight and lipid values. Of note, after a high-fat feeding for 16 weeks, <em>ApoE</em>^{<em>−/−</em>}<em>/TfR1</em>^{<em>+/−</em>} mice exhibited a reduction of the atherosclerotic areas in the aortic sinus and aorta compared with <em>ApoE</em>^{<em>−/−</em>} mice despite similar lipid values. In addition, <em>ApoE</em>^{<em>−/−</em>}<em>/TfR1</em>^{<em>+/−</em>} mice showed decreases in oxidative stress and macrophage accumulation in the aortic sinus and aorta compared with <em>ApoE</em>^{<em>−/−</em>} mice.</div></div><div><h3>Conclusions</h3><div>These results indicate that TfR1 deletion attenuates the development of atherosclerotic lesion formation in <em>ApoE</em>^{<em>−/−</em>} mice.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Pages 14-18"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population-based reference intervals for lipid function tests in pregnant and non-pregnant women in Nairobi City, Kenya","authors":"David Nzioka Mutua ,&nbsp;Eliud Nyaga Mwaniki Njagi ,&nbsp;George Owino Orinda","doi":"10.1016/j.athplu.2026.01.005","DOIUrl":"10.1016/j.athplu.2026.01.005","url":null,"abstract":"<div><h3>Background</h3><div>Accurate interpretation of clinical laboratory test results relies on the application of appropriate reference intervals, which differs between populations. Despite this, there is no Kenyan-derived reference values for clinical management of both pregnant and non-pregnant women, potentially leading to diagnostic misclassification. This study established age- and trimester-specific reference intervals for lipid function tests and compare them with the current practice cut-offs.</div></div><div><h3>Methods</h3><div>Lipid parameters were determined in non-pregnant and pregnant women aged 19–29 and 30–40 years, partitioned by trimester. The measured parameters included total cholesterol, low and density lipoproteins, triglycerides, non-high-density lipoproteins, and their ratios. Differences between groups were assessed using Kruskal-Wallis and Mann-Whitney U tests. Out-of-range analysis were performed between the newly developed reference intervals and the current practice reference values.</div></div><div><h3>Results</h3><div>Significant age- and trimester-specific differences were noted in total cholesterol, low-density lipoproteins, triglycerides, and lipid ratios (p &lt; 0.05), with incremental increases observed in later trimesters. High-density lipoproteins showed variable changes. Out-of-range comparison show significant misclassification: 54 % of pregnant women aged 30–40 years in the trimester two exceeded current low-density lipoproteins reference intervals, while 60 % were misclassified for triglycerides in third trimester. Remarkably, 100 % of women across all groups fell outside the standard high-density lipoproteins reference limits.</div></div><div><h3>Conclusion</h3><div>The current practice reference intervals are inappropriate for clinical assessment of pregnant and non-pregnant women in Nairobi, Kenya. Establishing age- and trimester-specific reference intervals provides a more accurate clinical decision-making tool, enhancing maternal care.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Pages 44-51"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-procedural C-reactive protein levels and carotid or intracranial artery restenosis: A systematic review and meta-analysis","authors":"Krishi Jain ,&nbsp;Hermann Pasha ,&nbsp;J.J. Coughlan ,&nbsp;Daniel O'Callaghan ,&nbsp;Niall Connolly ,&nbsp;Roisin Colleran ,&nbsp;Osama Soliman ,&nbsp;Robert A. Byrne ,&nbsp;Himanshu Rai","doi":"10.1016/j.athplu.2026.01.006","DOIUrl":"10.1016/j.athplu.2026.01.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Restenosis of the carotid or intracranial (IC) arteries, shown to be associated with increased risk of ischemic stroke, represents an unresolved clinical issue. Residual local and systemic inflammation at the time of the index revascularization, of which C-reactive protein (CRP) is a marker of, has been associated with coronary restenosis. Its association with carotid or IC restenosis post revascularization, however, remains uncertain. We therefore conducted a systematic review and a study-level meta-analysis investigating the association of pre-procedural CRP levels and the subsequent incidence of carotid and IC restenosis.</div></div><div><h3>Methods</h3><div>Online databases of PubMed, EMBASE, MEDLINE, Scopus, and Web of Science were systematically searched for articles published until August 31st, 2025. Pooled effect sizes were obtained from study-level standard mean differences (SMD) and their 95% confidence intervals (CI), employing a Z-test, with random effects for analysis.</div></div><div><h3>Results</h3><div>Out of 175 unique articles screened, 12 case-control studies, with a total sample of 2040 (325 restenosis cases/1715 no-restenosis controls), were included for quantitative synthesis. The pooled results demonstrated that pre-procedural CRP levels were associated with carotid or IC restenosis, with significantly higher pre-procedural CRP levels amongst the restenosis group in comparison to the no-restenosis group (SMD = 0.50, 95% CI = 0.11–0.89, p = 0.01). No apparent publication bias was detected either visually by Begg's funnel plot or Egger's test (p = 0.51). Leave-one-out sensitivity analysis supported the robustness of the results.</div></div><div><h3>Conclusions</h3><div>This meta-analysis suggests a significant association between pre-procedural CRP levels and the subsequent incidence of carotid and intracranial artery restenosis.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Pages 52-57"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statin treatment in routine clinical practice: Insights from the STATRIP physician survey","authors":"Panagiota Anyfanti ,&nbsp;Christina Antza ,&nbsp;Dimitrios Poulis ,&nbsp;Konstantinos Konstantaros ,&nbsp;Makrina Savvoulidou ,&nbsp;Georgios Styliadis ,&nbsp;Vasilios Kotsis","doi":"10.1016/j.athplu.2026.01.003","DOIUrl":"10.1016/j.athplu.2026.01.003","url":null,"abstract":"<div><h3>Background</h3><div>Statins remain to date the primary therapeutic option for dyslipidemia. However, a significant portion of patients with dyslipidemia fail to achieve optimal low-density lipoprotein targets for reasons often related to treating physicians. The aim of STAtin Treatment in Routine clinical Practice (STATRIP) survey was to report and quantify perceptions and common beliefs regarding treatment with statins, among physicians implicated in the primary and secondary care of patients with dyslipidemia.</div></div><div><h3>Methods and results</h3><div>This observational cross-sectional study was conducted using an online-distributed questionnaire, which was designed to cover a wide range of physicians’ knowledge and perceptions on treatment with statins. A total of 261 health care providers filled out the survey, mostly general practitioners and internists (93.5 %). Study participants clearly expressed their concerns regarding statin-related side effects, including fears on interactions with other medication, muscle aches and pain, increase in liver enzymes, and gastrointestinal disorders. Myalgias were observed by physicians in as many as 29.2 % of patients receiving rosuvastatin, and in as many as 26.5 % receiving atorvastatin. Combination lipid-lowering therapy with ezetimibe was reported by only 53.6 % of participants as a prevalent strategy for uncontrolled individuals. Only 58.6 % apply non-HDL cholesterol measurements in their clinical practice.</div></div><div><h3>Conclusions</h3><div>Our study provides a clear perspective of treating physicians regarding statin prescription patterns. Several misconceptions, especially regarding statin-related adverse effects, hold well among treating physicians. Insufficient implementation of dyslipidemia guidelines calls for more targeted educational interventions to achieve optimal management of patients with dyslipidemia.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Pages 28-33"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LDL-C lowering in patients treated with bempedoic acid in a real-world cohort","authors":"James Nelson ,&nbsp;LeAnne Bloedon ,&nbsp;Dave Lewandowski ,&nbsp;Muthiah Vaduganathan ,&nbsp;Maryam Ajose ,&nbsp;Mac Bonafede ,&nbsp;Evelyn Sarnes","doi":"10.1016/j.athplu.2026.01.007","DOIUrl":"10.1016/j.athplu.2026.01.007","url":null,"abstract":"<div><h3>Background</h3><div>Elevated low-density lipoprotein cholesterol (LDL-C) is directly associated with cardiovascular disease, with the risk level determined by the magnitude and duration of exposure. In routine practice, there are limited data on the expected LDL-C lowering with bempedoic acid (BA) alone or in combination with ezetimibe (BA + EZE).</div></div><div><h3>Methods</h3><div>Patients initiating BA or BA + EZE were identified in the Veradigm Network EHR linked to claims (index). LDL-C levels were evaluated at baseline, 3, 6, and 12 months. To further examine BA and BA + EZE efficacy, patients were stratified by background statin use (12 months pre-index) and by continuous index therapy use (no therapy gap &gt;45 days).</div></div><div><h3>Results</h3><div>Of the 900 BA and 615 BA + EZE patients identified, median baseline LDL-C was 137 mg/dL and 127 mg/dL, respectively. By 3 months, BA (21%) and BA + EZE (33%, <em>p</em> &lt; 0.0001 for both) were associated with significant reductions in median LDL-C levels. At baseline, only 6.3% of BA and 8.5% of BA + EZE patients had LDL-C &lt;70 mg/dL; by 3 months, this increased to 16.8% and 33.3%. Over 12 months, 18.0% and 27.5% of patients had LDL-C &lt;70 mg/dL. When stratified, the median reductions by 3 months highlighted use of BA and BA + EZE in patients without background statin use (BA: 24.2%; BA + EZE: 36.7%) and with continuous use (BA: 26.1%; BA + EZE: 40.2%).</div></div><div><h3>Conclusions</h3><div>Patients initiating BA and BA + EZE experienced early and sustained LDL-C improvements. The greatest reductions were in patients with continuous use and patients with no evidence of prior statin use, underscoring the importance of long-term adherence and treating patients not on statin therapy.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Pages 58-66"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147312093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poecilobdella manillensis ameliorates atherosclerosis by inhibiting endothelial cell pyroptosis","authors":"Chunxia Guo,&nbsp;Yudong Rao,&nbsp;Hao Zhou,&nbsp;Yiran Feng,&nbsp;Ganyu Deng,&nbsp;Lin Yang,&nbsp;Ying Zhang,&nbsp;Xueya Zhang","doi":"10.1016/j.athplu.2025.12.004","DOIUrl":"10.1016/j.athplu.2025.12.004","url":null,"abstract":"<div><h3>Objective</h3><div>Leeches and other herbs may improve atherosclerosis symptoms. This study explores <em>Poecilobdella manillensis</em>'effect on AS.</div></div><div><h3>Methods</h3><div>In vivo used high-fat diet + rabbit carotid balloon injury model, with <em>Poecilobdella manillensis</em> at 0.1, 0.4, 0.8 g/day. In vitro, aortic endothelial cells were treated with ox-LDL to establish AS model, then with animal group sera to assess P.manillensis effects on AS and explore mechanisms.</div></div><div><h3>Results</h3><div>The in vivo findings indicated that P.manillensis is capable of lowering blood lipid levels and exhibiting anti-thrombotic properties. Additionally, P.manillensis significantly alleviated pathological damage and lipid deposition in the common carotid artery, and reduced apoptosis of the common carotid artery smooth muscle cells. Further assays revealed that P.manillensis markedly decreased the levels of PI3K, p-AKT, NF-κB p65, NLRP3, Caspase-1, eNOS, GSDMD, IL-1β, and IL-18. In vitro results demonstrated that serum containing P.manillensis significantly enhanced cell activity and ATP production while decreasing the apoptosis rate, IL-1β, IL-18, LDH, and ROS, PI3K, p-AKT, NF-κB p65, NLRP3, Caspase-1, GSDMD, and ASC levels.</div></div><div><h3>Conclusion</h3><div>Both in vivo and in vitro studies have confirmed that P.manillensis ameliorates endothelial damage and inflammatory responses in AS, with involvement of the PI3K/AKT and NF-κB signaling pathways.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Pages 1-13"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to Neural network model outperforms conventional equations in LDL cholesterol estimation: A comparative study of 188,887 Chinese individuals with focus on hypertriglyceridemia [Atherosclerosis Plus, (62), December 2025, Pages 38-46]","authors":"Hao Xue ,&nbsp;Yu Lin ,&nbsp;Youlin Liu ,&nbsp;Lin Li ,&nbsp;Pengzhen Chen ,&nbsp;Mingyang Li ,&nbsp;Ling Ji ,&nbsp;Yong Xia","doi":"10.1016/j.athplu.2026.01.004","DOIUrl":"10.1016/j.athplu.2026.01.004","url":null,"abstract":"","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Page 43"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of abnormal phosphatidylcholine metabolism in endoplasmic reticulum stress-induced carotid artery plaque destabilization","authors":"Qifei Hu ,&nbsp;Haoran Zhang ,&nbsp;Xianwei Wang ,&nbsp;Jiaming Huang ,&nbsp;Xiaohui Jiang ,&nbsp;Mei Li ,&nbsp;Dong Chen","doi":"10.1016/j.athplu.2026.02.001","DOIUrl":"10.1016/j.athplu.2026.02.001","url":null,"abstract":"<div><h3>Background and aims</h3><div>The imbalance of carotid plaque stability is a key cause of acute cardiovascular and cerebrovascular events. Lipid metabolism disorder and endoplasmic reticulum stress (ERS) are both involved in the progression of atherosclerotic plaque. This study aims to reveal the role and molecular mechanism of abnormal phosphatidylcholine metabolism in ERS-induced carotid plaque instability, and to provide theoretical basis for plaque stabilization intervention.</div></div><div><h3><strong>Methods</strong></h3><div>With carotid plaques intima-media specimens as the research object, by HE staining is divided into a stable plaque group (group S) and unstable plaque group (U); The differences of metabolic profiles between the two groups were analyzed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The differential metabolites were screened by cluster heat map and volcano map. Metabolic pathway enrichment analysis and IPA pathway analysis were used to identify key pathways. Finally, Western blot and RT-qPCR were used to verify the protein and mRNA expression levels of key molecules in ERS pathway.</div></div><div><h3>Results</h3><div>Two groups of baseline characteristics have no statistical difference (P &gt; 0.05); PCA and OPLS-DA showed that the metabolic profiles of group S and group U were significantly separated. A total of 198 potential biomarkers were identified. Among them, changes in phospholipid metabolites (including phosphatidylcholine) were significant, and these are the core markers for differentiating plaque stability. Metabolic pathway enrichment analysis showed that glycerophospholipid metabolic pathway was the key core pathway regulating plaque stability. The protein and mRNA expressions of key molecules of ERS pathway (GRP78, ATF6, PERK, CHOP and IRE1) in group U were significantly higher than those in group S.</div></div><div><h3>Conclusion</h3><div>Abnormal metabolism of phosphatidylcholine can drive the transformation of carotid plaques to an unstable phenotype by activating the ER stress (ERS) pathway (especially the PERK/CHOP branch pathway); this study verified the association mechanism between abnormal phosphatidylcholine metabolism and the activation of the ER stress pathway and the occurrence of unstable carotid plaques, providing experimental evidence for the study of the mechanism of unstable carotid plaques and the formulation of targeted clinical intervention strategies<u>.</u></div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Pages 67-76"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}