Atherosclerosis plus最新文献

{"title":"Fucosterol exerts an anti-atherosclerotic action via NF-κB and p38/Erk MAPK signaling pathways","authors":"Tiancheng Liu ,&nbsp;Mengli Zhang ,&nbsp;Xian Wu ,&nbsp;Zhenxing Liu ,&nbsp;Huan Peng ,&nbsp;Feng Gui ,&nbsp;Wen Xiong ,&nbsp;Qijuan Liu ,&nbsp;Guojun Du ,&nbsp;Bo Liu ,&nbsp;Chenchen Zhang ,&nbsp;Junfeng Ma ,&nbsp;Quan Yuan ,&nbsp;Wei Li ,&nbsp;Zhen Chen","doi":"10.1016/j.athplu.2025.05.001","DOIUrl":"10.1016/j.athplu.2025.05.001","url":null,"abstract":"<div><h3>Background</h3><div>Fucosterol is a sterol isolated from brown algae and has various biological properties, such anti-inflammatory and antidiabetic effects. In this study, we investigated the anti-atherosclerosis effects of fucosterol <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Methods</h3><div>ApoE^−/− mice were fed a high fat diet for 12 weeks with or without fucosterol treatment. H&amp;E staining and Oil Red O staining were performed to detect atherosclerotic lesion and lipid content in the aorta of mice. The lipid metabolism indexes in the mouse serum were measured. Macrophage infiltration into the aortic wall was detected using immunohistochemistry of CD68. Human umbilical vein endothelial cells (HUVECs) were treated with 100 μg/mL ox-LDL to establish a cell model of atherosclerosis <em>in vitro</em>. The expression and protein levels of adhesion molecules and inflammatory cytokines in the aorta and HUVECs were measured using RT-qPCR and western blot, respectively. The levels of oxidative stress-related markers in the mouse serum and HUVECs were measured using corresponding detection kits. The effects of fucosterol on the viability and apoptosis of HUVECs were detected using CCK-8 and flow cytometry, respectively. The levels of NF-κB and p38/Erk MAPK pathway-related proteins in HUVECs were assessed by western blot.</div></div><div><h3>Results</h3><div>Fucosterol reduced atherosclerotic plaques and lipid levels in apoE^−/− mice. Fucosterol alleviated macrophage infiltration, inflammatory response, and oxidative stress in apoE^−/− mice. The ox-LDL-induced inflammatory response, oxidative stress, and apoptosis in HUVECs were attenuated by fucosterol. Additionally, fucosterol reduced the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) in <em>vivo</em> and <em>in vitro</em>. Moreover, the ox-LDL-induced activation of the NF-κB and p38/Erk MAPK signaling in HUVECs was suppressed by fucosterol.</div></div><div><h3>Conclusion</h3><div>The current investigation revealed that fucosterol attenuates atherosclerotic plaques in apoE^−/− mice through the inhibition of hyperlipidemia, inflammation, and oxidative stress.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"60 ","pages":"Pages 51-59"},"PeriodicalIF":1.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131755","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":"Plasma apolipoprotein concentrations and occurrence of cardiovascular events in the general population: an exploratory analysis","authors":"Avedis Torossian ,&nbsp;Annelise Genoux ,&nbsp;Zichun Cai ,&nbsp;Nathan Jolivet ,&nbsp;Mikaël Croyal ,&nbsp;Arsênio Rodrigues Oliveira ,&nbsp;Sébastien Dejean ,&nbsp;Nathalie Viguerie ,&nbsp;Cendrine Cabou ,&nbsp;Bertrand Perret ,&nbsp;Jean Ferrières ,&nbsp;Vanina Bongard ,&nbsp;Laurent O. Martinez","doi":"10.1016/j.athplu.2025.04.003","DOIUrl":"10.1016/j.athplu.2025.04.003","url":null,"abstract":"<div><h3>Background and aims</h3><div>The role of many apolipoproteins in cardiovascular disease (CVD) pathophysiology and their predictive potential remains unclear. This study examined the association between plasma concentrations of a broad panel of apolipoproteins and the occurrence of cardiovascular events in a general population.</div></div><div><h3>Methods</h3><div>A nested case-control study was conducted within a cohort from Southwestern France. Baseline concentrations of apolipoproteins A-I, A-II, A-IV, B100, C-I, C-II, C-III, D, E, H, J, L1 and M were analyzed in 65 cases who experienced a cardiovascular event during the follow-up period, and in 65 controls matched for age and sex (mean age 60.9 ± 10.7 years; 66.9 % men; median follow up 9.3 years for controls, 6.2 years for cases). Baseline correlations were assessed using Spearman's coefficients.</div><div>Logistic regression and partial least squares discriminant analysis (PLS-DA) were used to evaluate associations with the occurrence of cardiovascular events.</div></div><div><h3>Results</h3><div>Concentrations of apolipoproteins A-I, A-IV, C-I, D, H, J and M differed significantly between cases and controls. All expect apoM remained independently associated with cardiovascular events after adjustment for known risk factors. Additionally, PLS-DA revealed that the entire apolipoprotein panel explained 64 % of variance in case-control status with 60 % predictive accuracy, with apolipoproteins D, J, A-IV, H, and C-I contributing the most to group discrimination.</div></div><div><h3>Conclusions</h3><div>This study identifies a novel panel of apolipoproteins (A-I, A-IV, C-I, D, H, and J) whose levels are associated with occurrence of cardiovascular diseases, independently of traditional risk factors. Further research is needed to confirm these findings and explore underlying mechanisms.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"60 ","pages":"Pages 35-42"},"PeriodicalIF":1.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069266","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":"Association of dietary preferences with cardiovascular disease: a Mendelian randomization study","authors":"Mia D. Lee ,&nbsp;Benjamin F. Voight","doi":"10.1016/j.athplu.2025.04.002","DOIUrl":"10.1016/j.athplu.2025.04.002","url":null,"abstract":"<div><h3>Background and aims</h3><div>Susceptibility to cardiovascular disease (CVD) is driven by genetic and environmental risk factors. Diet is a modifiable and largely environmental risk factor for CVD. Genetic factors associated with a variety of dietary preferences revealed via recent genome-wide association studies (GWAS) allow further investigate the role of diet in liability to disease that has been limited to observational and epidemiologic studies with mixed findings.</div></div><div><h3>Method</h3><div>We obtained publicly available genome-wide association data for 38 dietary preference traits and seven common CVDs to investigate causal hypotheses between diet as the exposure to CVD as outcomes using the statistical framework of Mendelian randomization (MR) for hypothesis testing and sensitivity analyses. We also conducted mediation analyses to evaluate the effects of dietary preferences on CVDs to elucidate potential causal graphs and estimate the effects of dietary preferences mediated by potential mediators.</div></div><div><h3>Results</h3><div>Across all methods, we identified 10 significant causal effects, which included eight dietary preferences across three CVD endpoints (Bonferroni-corrected P &lt; 1.88 × 10⁻⁴). In sensitivity MR and mediation analysis, we observed that obesity - quantified by body mass index (BMI) - was a common mediator that contributed to many of these observed effects. We also found that educational attainment was an exclusive, additional mediator for the effect of preference for muesli with risk to peripheral artery disease (PAD).</div></div><div><h3>Conclusions</h3><div>Our results provide genetic evidence for a link between diet and CVD that aligns with obesity-mediated risk of CVD in individuals in relation to their specific preferences for food.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"60 ","pages":"Pages 43-50"},"PeriodicalIF":1.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107075","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":"Trends of atherosclerosis-related mortality in adults with diabetes: A cross-sectional analysis of U.S. national data","authors":"Yusuf Hasan Ali ,&nbsp;Fakhar Latif ,&nbsp;Fatimah Hoda ,&nbsp;Azeem Hassan ,&nbsp;Huda Ahmed ,&nbsp;Raheel Ahmed ,&nbsp;Vikash Jaiswal","doi":"10.1016/j.athplu.2025.04.001","DOIUrl":"10.1016/j.athplu.2025.04.001","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus is a rapidly growing global health issue, projected to affect 643 million adults by 2030. Atherosclerosis, a prevalent complication of diabetes, significantly contributes to morbidity and mortality among affected individuals. This study aimed to analyze mortality trends associated with atherosclerosis in diabetic patients aged ≥45 years, with particular focus on variations by sex, race, urban-rural classification, and geographical regions in the US from 1999 to 2020.</div></div><div><h3>Methods</h3><div>We conducted a study using data from the CDC WONDER database, identifying atherosclerosis-related deaths in diabetic patients. We calculated age-adjusted mortality rates (AAMRs) per 100,000 population and analyzed trends over time using Joinpoint regression to assess annual percentage changes (APC) and average annual percentage changes (AAPC).</div></div><div><h3>Results</h3><div>A total of 674,582 atherosclerosis-related deaths were recorded in diabetic patients from 1999 to 2020, with a higher prevalence in men (57.40 %). The majority of deaths occurred in NH White individuals (81.70 %). Overall, AAMRs declined from 32.8 in 1999 to 25.8 in 2020. A significant decrease was observed from 1999 to 2014 (APC: −2.61, p &lt; 0.05), followed by stability (2014–2018) and a subsequent rise (APC: 6.97, p &lt; 0.05) till 2020. Sex-stratified analysis indicated persistently higher AAMRs in men, with a significant increase from 2018 to 2020 (APC: 7.33, p &lt; 0.05). Racial disparities were evident, with NH Black individuals demonstrating the highest AAMRs. Geographic analysis revealed higher AAMRs in nonmetropolitan areas, with notable state-level variations. All census regions exhibited an initial decline, followed by a significant rise in AAMRs post-2018 (p &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>Despite initial declines, recent trends indicate a resurgence in atherosclerosis-related mortality among diabetic patients, particularly in specific racial groups, rural areas, and certain regions. These findings underscore the need for targeted interventions to address disparities and improve cardiovascular outcomes in diabetic populations.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"60 ","pages":"Pages 27-34"},"PeriodicalIF":1.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935996","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":"ApoE [−/−] CA1-overexpressing knock-in mice aggravated atherosclerosis by increasing M1 macrophages","authors":"Jinbao Zong ,&nbsp;Changyuan Wang ,&nbsp;Hongji Zhou ,&nbsp;Yu Song ,&nbsp;Kehua Fang ,&nbsp;Xiaotian Chang","doi":"10.1016/j.athplu.2025.03.003","DOIUrl":"10.1016/j.athplu.2025.03.003","url":null,"abstract":"<div><h3>Background</h3><div>Carbonic anhydrase I (CA1) has been reported to be a diagnostic and therapeutic target for atherosclerosis (AS). This study aimed to verify the essential role of CA1 in AS progression in CA1-overexpressing mice.</div></div><div><h3>Methods</h3><div>A ApoE [−/−] CA1-overexpressing knock-in mouse model was constructed via CRISPR/Cas9-mediated genome engineering. AS was then induced in these transgenic mice via the administration of a high-fat diet, and a second group simultaneously received treatment with methazolamide (MTZ), a carbonic anhydrase inhibitor.</div></div><div><h3>Results</h3><div>Compared with ApoE [−/−] mice without CA1 overexpression, CA1-overexpressing mice had a greater average body weight, regardless of whether their treatment with MTZ or their AS induction status. Sudan IV, hematoxylin and eosin and Oil Red O staining revealed more plaques and fat deposits in the cardiac aortas of CA1-overexpressing mice than in those of ordinary ApoE−/− mice when AS was induced. Moreover, the atherogenic index; low-density lipoprotein, total cholesterol and triglyceride levels were significantly elevated, and high-density lipoprotein levels were declined in the peripheral blood of CA1-overexpressing mice than in that of ordinary ApoE [−/−] mice, regardless of whether these animals were induced to AS. Immunohistochemistry, <em>Von Kossa</em> staining and fluorescence immunohistochemistry revealed increases in CA1 expression, calcium deposition and M1 macrophages in the aortic tissues of CA1-overexpressing mice with AS. MTZ treatment significantly suppressed AS pathologies in the above experiments.</div></div><div><h3>Conclusion</h3><div>These findings revealed aggravated AS in ApoE [−/−] CA1-overexpressing mice and suggest that CA1 aggravates AS by increasing M1-type macrophages, a proinflammatory macrophage subtype.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"60 ","pages":"Pages 6-19"},"PeriodicalIF":1.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world management of hypercholesterolemia in patients after acute coronary syndrome in Greece","authors":"Despoina Massia ,&nbsp;Periklis Giovas ,&nbsp;Nikolaos Papadopoulos ,&nbsp;Georgios Katsimagklis ,&nbsp;Evangelos Pissimisis ,&nbsp;Sotirios Patsilinakos ,&nbsp;Evgenia Pappa ,&nbsp;Giannis Baltogiannis ,&nbsp;Nikolaos Kouremenos ,&nbsp;Christos Dontas ,&nbsp;Evangelos Liberopoulos","doi":"10.1016/j.athplu.2025.03.002","DOIUrl":"10.1016/j.athplu.2025.03.002","url":null,"abstract":"<div><h3>Background</h3><div>Prompt initiation of lipid-lowering therapy (LLT) following acute coronary syndrome (ACS) is crucial for preventing secondary cardiovascular events. However, there are gaps in clinical implementation of the 2019 ESC/EAS guideline-recommended low-density lipoprotein cholesterol (LDL-C) goal of &lt;55 mg/dL in patients post-ACS.</div></div><div><h3>Methods</h3><div>This multicenter, real-world, retrospective, 12-month study of adult patients in Greece hospitalized for ACS from September 2019 to November 2022 assessed the attainment of target LDL-C (&lt;55 mg/dL) during the first year post-ACS. Eligible patients had elevated LDL-C at hospitalization (&gt;130 mg/dL if LLT naïve; &gt;100 mg/dL if on statin monotherapy; &gt;70 mg/dL if on a statin plus ezetimibe) and ≥1 LDL-C measurement within 12 months post-ACS.</div></div><div><h3>Results</h3><div>Overall, 212 eligible patients of mean (SD) age 59.9 (±11.1) years were enrolled. Type 2 diabetes and hypertension were reported in 19.8 % (42/212) and 50.9 % (108/212) of patients, respectively. Median (Q1, Q3) LDL-C was 138.0 (106.5, 158.0) mg/dL at hospitalization (n = 212). In patients with LDL-C availability at 12 months posthospitalization (n = 197), median (Q1, Q3) LDL-C was 64.0 (53.0, 76.0) mg/dL, with 27.9 % of patients (55/197) attaining LDL-C &lt;55 mg/dL. Although 73.9 % of patients (199/212) were discharged from the hospital on statin monotherapy, 50 % of patients (106/212) were receiving statin-ezetimibe LLT and 1.4 % (3/212) were receiving statin-ezetimibe-PCSK9 inhibitor LLT 12 months posthospitalization.</div></div><div><h3>Conclusion</h3><div>LDL-C goal attainment is suboptimal in the first year after ACS hospitalization in Greece, indicating an unmet need to improve the treatment of patients with hypercholesterolemia during the post-ACS period by optimizing lipid management through earlier LLT intensification.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"60 ","pages":"Pages 20-26"},"PeriodicalIF":1.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A male patient with pseudoxanthoma elasticum caused by isodisomy of chromosome 16 containing a nonsense variant of the ABCC6 gene: A quarter-century treatment experience","authors":"Minoru Wakasa ,&nbsp;Chihiro Nakagawa ,&nbsp;Taka-aki Takamura ,&nbsp;Kosuke Fujibayashi ,&nbsp;Hironobu Akao ,&nbsp;Michihiko Kitayama ,&nbsp;Akira Shimizu ,&nbsp;Yo Niida ,&nbsp;Kouji Kajinami","doi":"10.1016/j.athplu.2025.03.001","DOIUrl":"10.1016/j.athplu.2025.03.001","url":null,"abstract":"<div><div>Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive disorder characterized by fragmentation and calcification of the elastic fibers of the skin, eyes, and various arteries with highly variable clinical expression. PXE is predominantly caused by pathogenic variants of the <em>ABCC6</em> gene, which encodes the ABCC6 efflux transporter; however, the precise mechanism responsible for clinical manifestation remains unclear. We herein report the case of a male patient with PXE with premature coronary stenosis as his first presentation requiring catheter intervention, in association with typical ocular and skin lesions; the latter was confirmed histologically. A molecular analysis revealed an isodisomy of 6.8 Mb in the 16p13.11 region containing the nonsense mutation p.(Gln199Ter) in the <em>ABCC6</em> gene. We also describe the 25-year clinical course of this case, while focusing on cardiovascular lesions.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"60 ","pages":"Pages 1-5"},"PeriodicalIF":1.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HDL-replacement therapy: From traditional to emerging clinical applications","authors":"Cesare Riccardo Sirtori ,&nbsp;Giulia Cincotto ,&nbsp;Sofia Castiglione ,&nbsp;Chiara Pavanello","doi":"10.1016/j.athplu.2025.02.001","DOIUrl":"10.1016/j.athplu.2025.02.001","url":null,"abstract":"<div><div>The unique and multifaceted properties of high-density lipoproteins (HDL)—ranging from cholesterol efflux to anti-inflammatory, anti-oxidant, and immunomodulatory effects—have prompted their direct use, particularly in cardiovascular ischemic conditions.</div><div>Recent advances have extended the interest in HDL-based treatments to novel applications, from improving stent biocompatibility, to treatment of heart failure to central nervous system (CNS) disorders. Strategies to harness HDL's therapeutic potential have evolved from the direct use of isolated HDL in animal models to reconstituted HDL (rHDL) in humans. For these latter, the use of isolated apoA-I associated with different phospholipids has been the most frequent approach, also involving apparently beneficial mutants, such as the apo A-I Milano (AIM).</div><div>From the initial very promising results, particularly with this mutant in coronary patients, later studies have mostly been non-confirmatory, although issues such as possible inadequate dose/response and unexpected immunological properties have come to light. Most recently a study on isolated plasma HDL in coronary patients (AEGIS-II) provided overall negative findings, but a clear fall of major cardiovascular events was recorded when restricting analysis to hypercholesterolemic patients.</div><div>Emerging approaches, including gene therapy and plant-derived recombinant HDL formulations, hold promise for enhancing the accessibility and efficacy of HDL-based interventions. At this time, an improved approach to heart failure treatment also appears feasible, and a better understanding of the role played by HDL in the CNS may lead to significant improvements in the handling of some dramatic diseases at this level. While challenges persist, the evolving landscape of HDL replacement therapies offers hope for significant progress in addressing both cardiovascular and non-cardiovascular conditions.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"59 ","pages":"Pages 68-79"},"PeriodicalIF":1.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of edoxaban monotherapy after bioabsorbable polymer everolimus-eluting stent implantation in a human-like coronary atherosclerotic porcine model","authors":"Daisuke Kitano ,&nbsp;Suguru Migita ,&nbsp;Yuxin Li ,&nbsp;Yutaka Koyama ,&nbsp;Katsunori Fukumoto ,&nbsp;Sayaka Shimodai-Yamada ,&nbsp;Akira Onishi ,&nbsp;Daiichiro Fuchimoto ,&nbsp;Shunichi Suzuki ,&nbsp;Yoshiyuki Nakamura ,&nbsp;Atsushi Hirayama ,&nbsp;Hiroyuki Hao ,&nbsp;Yasuo Okumura","doi":"10.1016/j.athplu.2025.01.002","DOIUrl":"10.1016/j.athplu.2025.01.002","url":null,"abstract":"<div><h3>Background</h3><div>The combination of antiplatelet and antithrombotic drugs increases the risk of bleeding in patients with atrial fibrillation after coronary drug-eluting stent (DES) implantation. However, the appropriateness of direct-acting oral anticoagulant (DOAC) monotherapy at the time of stent implantation remains uncertain. The objective of this study was to evaluate the safety and efficacy of DOAC monotherapy, specifically using factor Xa inhibitors such as edoxaban, in a low-density lipoprotein receptor knockout (LDL-R^−/−) miniature pig model of human-like unstable coronary plaques compared to conventional dual-antiplatelet therapy (DAPT).</div></div><div><h3>Methods</h3><div>We evaluated the safety and efficacy of edoxaban monotherapy in the LDL-R^−/− pig model with human-like unstable coronary plaques induced by a high-cholesterol, high-fat diet. Animals underwent DES implantation, followed by four weeks of treatment with either edoxaban monotherapy (3 mg/kg/day) or the DAPT regimen (aspirin 100 mg/day and clopidogrel 75 mg/day). Outcomes were assessed by optical coherence tomography (OCT), virtual histology intravascular ultrasound (iMap-IVUS), and histology. Key endpoints included in-stent thrombus formation, neointimal thickness, and coronary plaque composition.</div></div><div><h3>Results</h3><div>Edoxaban monotherapy demonstrated a significantly thinner neointimal layer (120.0 [92.5–160.0] μm vs. 210.0 [180.0–240.0] μm, <em>p</em> &lt; 0.001) and smaller neointimal area (1.06 [0.82–1.46] mm² vs. 1.84 [1.61–2.24] mm², <em>p</em> &lt; 0.001) compared to DAPT. Neointimal coverage, fibrin deposition, and inflammatory cell infiltration were comparable between groups. No in-stent thrombi were observed in either group. iMap-IVUS findings indicated that edoxaban monotherapy significantly suppressed the increase in lipidic and necrotic plaque area while promoting fibrotic area expansion.</div></div><div><h3>Conclusions</h3><div>Edoxaban monotherapy demonstrated superior efficacy in suppressing neointimal hyperplasia and stabilizing coronary plaques compared to DAPT with equivalent safety in preventing in-stent thrombus formation. These results provide important preclinical evidence supporting the potential of DOAC monotherapy as an antithrombotic strategy after DES implantation and warrant further investigation in clinical trials.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"59 ","pages":"Pages 59-67"},"PeriodicalIF":1.4,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143263756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Inclisiran: Early LDL-C target achievement in a real-life population”","authors":"Francesco Briani ,&nbsp;Mauro Bagli ,&nbsp;Gabriele Venturi ,&nbsp;Francesco Bacchion ,&nbsp;Antonio Mugnolo","doi":"10.1016/j.athplu.2025.01.001","DOIUrl":"10.1016/j.athplu.2025.01.001","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with atherosclerotic cardiovascular diseases. Inclisiran, a small interfering RNA, has been observed to effectively and sustainably reduce LDL-C in large randomized controlled trials (RCTs); however, real-world data on its short-term efficacy and use are limited. This study aims to assess the efficacy and safety of inclisiran in a real-life population within one month from the first administration.</div></div><div><h3>Methods</h3><div>This observational, single-center, retrospective cohort study included patients affected by dyslipidemia who could not achieve their LDL-C target despite a maximum tolerated oral lipid-lowering therapy (LLT). 284 mg Inclisiran was subcutaneously administered. Blood samples were collected before the inclisiran administration and at week and one month afterward with the aim toevaluate achievement of LDL-C targets at these time intervals (primary endpoint) and reduction in LDL-C levels (secondary endpoint).</div></div><div><h3>Results</h3><div>From September 2022 to December 2023, inclisiran was administered to 33 patients at Mater Salutis Hospital. After exclusion of two patients due to statin therapy modification or discontinuation during follow-up, a final number of 31 patients were included. At a median follow-up of 32 (IQ_1-3 30–37) days, 21 (67.7 %) patients reached their LDL-C target (primary endpoint). At 7 days, LDL-C mean value decreased from 123.6 ± 42.1 mg/dl to 97.9 ± 53.6 mg/dl, (p &lt; 0.001), with a 29.9 ± 20.6 % reduction. At 32 days, LDL-C mean value declined to 58.5 ± 42.8 mg/dl (p &lt; 0.001), with a 56.9 ± 20.9 % reduction.</div></div><div><h3>Conclusion</h3><div>In a real-life single center population, inclisiran safely led to LDL-C target achievement within one month. Significantly reduction of LDL-C levels were already present in the early days after the first administration.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"59 ","pages":"Pages 54-58"},"PeriodicalIF":1.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143263754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}