Atherosclerosis最新文献

{"title":"Lipidic contents within calcified plaques: Characteristics and response to LDL-C<55 mg/dL on multi-modality imaging","authors":"Kentaro Mitsui ,&nbsp;Yu Kataoka ,&nbsp;Stephen J. Nicholls ,&nbsp;Eri Kiyoshige ,&nbsp;Kunihiro Nishimura ,&nbsp;Rishi Puri ,&nbsp;Kota Murai ,&nbsp;Kenichiro Sawada ,&nbsp;Hideo Matama ,&nbsp;Takamasa Iwai ,&nbsp;Satoshi Honda ,&nbsp;Masashi Fujino ,&nbsp;Kazuhiro Nakao ,&nbsp;Kensuke Takagi ,&nbsp;Shuichi Yoneda ,&nbsp;Fumiyuki Otsuka ,&nbsp;Kensaku Nishihira ,&nbsp;Itaru Takamisawa ,&nbsp;Yasuhide Asaumi ,&nbsp;Kenichi Tsujita ,&nbsp;Teruo Noguchi","doi":"10.1016/j.atherosclerosis.2025.120500","DOIUrl":"10.1016/j.atherosclerosis.2025.120500","url":null,"abstract":"<div><h3>Background and aims</h3><div>Calcified plaques have traditionally been regarded as advanced and quiescent atheroma. However, pathological studies indicate lipid content within calcified plaques, suggesting that calcified plaques may harbor active lipidic contents. This study evaluated lipidic plaque content in calcified lesions <em>in vivo</em> using IVUS, OCT and near-infrared spectroscopy (NIRS).</div></div><div><h3>Methods</h3><div>We analyzed 325 cross-sectional frames at 65 calcified lesions in 58 CAD patients from the REASSURE-NIRS registry (NCT04864171). OCT-derived calcification measures, and the arc of NIRS-derived yellow signals within calcification (YSC) were measured. Plaque features were compared between cross-sectional frames with YSC arc &lt; and ≥63° (=median).</div></div><div><h3>Results</h3><div>The median calcification arc was 224° (statin = 78 %, LDL-C = 81.5 mg/dL), and 73.8 % of images exhibited calcification arc ≥180°. Any YSC was observed at 84.3 % of analyzed frames. YSC arc ≥63° was associated with thinner (743 ± 276 vs. 882 ± 247 μm, p &lt; 0.001) and deeper calcification (median:50 vs. 30 μm, p = 0.002), whereas the frequency of macrophage (16.6 % vs. 11.7 %, p = 0.265), microvessels (0.6 % vs. 0.6 %, p = 1.000) and cholesterol crystals (1.2 % vs. 0.0 %, p = 0.498) did not differ between two groups. Multivariate analysis identified calcification thickness (β = −0.446, 95 % CI = −0.661–0.231, p &lt; 0.001) as an independent predictor of YSC arc ≥63°, whereas calcification arc (β = 0.000, 95 % CI = −0.001–0.001, p = 0.788) and depth (β = −0.592, 95 % CI = −1.408–0.224, p = 0.155) were not. Notably, LDL-C&lt;55 mg/dL was associated with larger calcification arc (p &lt; 0.001), but the YSC arc was not necessarily smaller despite achieving LDL-C&lt;55 mg/dL (p = 0.671).</div></div><div><h3>Conclusion</h3><div>Lipidic contents existed at calcified lesions exhibiting thinner calcification. This lipidic feature at calcified lesions less likely undergo changes in response to LDL-C&lt;55 mg/dL.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"413 ","pages":"Article 120500"},"PeriodicalIF":5.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131140","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":"Genome-wide gene-sleep interaction study identifies novel lipid loci in 732,564 participants","authors":"Raymond Noordam ,&nbsp;Wenyi Wang ,&nbsp;Pavithra Nagarajan ,&nbsp;Heming Wang ,&nbsp;Michael R. Brown ,&nbsp;Amy R. Bentley ,&nbsp;Qin Hui ,&nbsp;Aldi T. Kraja ,&nbsp;John L. Morrison ,&nbsp;Jeffrey R. O'Connel ,&nbsp;Songmi Lee ,&nbsp;Karen Schwander ,&nbsp;Traci M. Bartz ,&nbsp;Lisa de las Fuentes ,&nbsp;Mary F. Feitosa ,&nbsp;Xiuqing Guo ,&nbsp;Xu Hanfei ,&nbsp;Sarah E. Harris ,&nbsp;Zhijie Huang ,&nbsp;Mart Kals ,&nbsp;Diana van Heemst","doi":"10.1016/j.atherosclerosis.2025.120603","DOIUrl":"10.1016/j.atherosclerosis.2025.120603","url":null,"abstract":"<div><h3>Background and aims</h3><div>Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets.</div></div><div><h3>Methods</h3><div>We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) total sleep time were defined by the extreme 20 % of the age- and sex-standardized values within each cohort. Based on cohort-level summary statistics data, we performed meta-analyses for one-degree of freedom tests of interaction and two-degree of freedom joint tests of the SNP-main and -interaction effect on lipid levels.</div></div><div><h3>Results</h3><div>The one-degree of freedom variant-sleep interaction test identified 10 novel loci (P_int&lt;5.0e-9), and we additionally identify 7 loci within the two-degree of freedom analyses (P_joint&lt;5.0e-9 in combination with P_int&lt;6.6e-6). Multiple loci, including those mapped to <em>APSH</em> (target for aspartic and succinic acid) and <em>SLC8A1</em> showed biological plausibility and druggability potential based on literature.</div></div><div><h3>Conclusions</h3><div>Collectively, the 17 (9 with short and 8 with long sleep) loci provided evidence into the biomolecular mechanisms underlying sleep-associated lipid changes, including potential involvement of the vitamin D receptor pathway. Collectively, these findings may contribute developing novel interventions for treating dyslipidemia in people with sleep disturbances.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"412 ","pages":"Article 120603"},"PeriodicalIF":5.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653337","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":"AI-ECG age predicts carotid atherosclerotic plaque volume and progression","authors":"D. Pavluk ,&nbsp;M. Schreinlechner ,&nbsp;S. Proell ,&nbsp;F. Theurl ,&nbsp;P. Marschang ,&nbsp;M. Noflatscher ,&nbsp;F. Hofer ,&nbsp;C. Dlaska ,&nbsp;A. Bauer","doi":"10.1016/j.atherosclerosis.2025.120592","DOIUrl":"10.1016/j.atherosclerosis.2025.120592","url":null,"abstract":"<div><h3>Background and aims</h3><div>AI derived biological age from surface ECGs (AI ECG age) has shown prognostic value beyond chronological age. We hypothesized that AI ECG age reflects atherosclerotic burden as indicated by carotid plaque volume (PV).</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 101 patients with cardiovascular disease or ≥1 risk factor from a prospective single-center cohort (NCT01895725) on carotid atherosclerosis progression. Carotid plaque volume (PV) was measured by standardized 3D ultrasound at baseline and at ∼12-month intervals (median follow-up 1091 days). AI ECG age was derived from standard 10-s 12-lead ECGs using a validated deep neural network. Associations between AI ECG age, Δage (AI ECG age – chronological age), and PV were assessed by correlation, regression, and ROC analyses. At baseline, 101 patients had both ECG and 3D ultrasound; follow-up PV was available for 95, 88, and 80 patients at 1, 2 and 3 years, respectively.</div></div><div><h3>Results</h3><div>AI ECG age and chronological age correlated with PV (r = 0.54 and r = 0.48, both p &lt; 0.001). In multivariable linear regression, AI ECG age was independently associated with PV (β = 6.95, 95 %CI: 2.88–11.01, p = 0.001), whereas chronological age was not (p = 0.120). Adding Δ age to a model with age, sex, lipid and inflammatory markers improved AUC from 0.77 to 0.82 and enhanced net reclassification (NRI = 0.48, p = 0.017). AI-ECG age predicted PV progression over time (β = 1.83, 95 %CI: 0.42 to 4.09, p = 0.042), independent of chronological age.</div></div><div><h3>Conclusion</h3><div>AI ECG age correlates more closely with carotid plaque burden than chronological age. Its divergence from chronological age independently predicts plaque progression, supporting AI ECG age as an accessible adjunct for vascular risk assessment.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"412 ","pages":"Article 120592"},"PeriodicalIF":5.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622637","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":"Physical activity in carotid atherosclerotic patients blunts monocyte pro-inflammatory processes: a randomised controlled trial","authors":"Mathilde Mura ,&nbsp;Amandine Thomas ,&nbsp;Michèle Weiss-Gayet ,&nbsp;Laurie Josset ,&nbsp;Chantal L. Rytz ,&nbsp;Emeraude Rivoire ,&nbsp;Marie Chambion-Diaz ,&nbsp;Nellie Della-Schiava ,&nbsp;Matthieu Arsicot ,&nbsp;Anne Long ,&nbsp;Bénédicte Chazaud ,&nbsp;Antoine Millon ,&nbsp;Vincent Pialoux","doi":"10.1016/j.atherosclerosis.2025.120589","DOIUrl":"10.1016/j.atherosclerosis.2025.120589","url":null,"abstract":"<div><h3>Background and aims</h3><div>Up to 25 % of ischemic strokes are the consequence of a ruptured vulnerable carotid atherosclerotic plaque. Circulating pro-inflammatory classical and intermediate monocytes are known predictors of ischemic events and cardiovascular death. Interestingly, chronic physical activity can decrease inflammation, and is thereby associated with a reduction in pro-inflammatory monocytes.</div></div><div><h3>Methods</h3><div>In a randomized, controlled and monocentric trial, we recruited 56 patients (71 ± 8 years old) with asymptomatic carotid stenosis of ≥50 % who were ineligible for carotid endarterectomy. Blood analyses were completed to assess the phenotype of monocytes, as well as a multiplex assay and colorimetric assay for cytokines concentration and redox status, respectively.</div></div><div><h3>Results</h3><div>Classical monocyte count was increased in the control arm, while it remained stable in response to the physical activity intervention (−5215 ± 2307, [95 %CI -9878 to −551], p = 0.03). Moreover, the expression of most of pro-inflammatory cytokines was down-regulated in response to the physical activity intervention, while it was increased in the control arm.</div></div><div><h3>Conclusions</h3><div>The stabilization of classical monocytes and down-regulation of the expression of pro-inflammatory cytokines in response to the physical activity intervention suggest that chronic physical activity alleviate the pro-inflammatory state, and might thereby reduce carotid plaque vulnerability and the subsequent risk of ischemic events. These results highlight that home-based physical activity intervention is an efficient clinical care that induce biological changes in carotid atherosclerotic patients.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"412 ","pages":"Article 120589"},"PeriodicalIF":5.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145555130","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":"Associations of long-term cumulative C-reactive protein and glycoprotein acetyls concentrations in childhood, adolescence and adulthood with adulthood retinal microvascular structure","authors":"Oskari Repo ,&nbsp;Markus Juonala ,&nbsp;Harri Niinikoski ,&nbsp;Suvi Rovio ,&nbsp;Juha Mykkänen ,&nbsp;Carol Y. Cheung ,&nbsp;Mika Ala-Korpela ,&nbsp;Hanna Vaahtoranta-Lehtonen ,&nbsp;Jaakko Nevalainen ,&nbsp;Antti Jula ,&nbsp;Mika Kähönen ,&nbsp;Terho Lehtimäki ,&nbsp;Tomi P. Laitinen ,&nbsp;Tapani Rönnemaa ,&nbsp;Jorma Viikari ,&nbsp;Olli Raitakari ,&nbsp;Robyn Tapp ,&nbsp;Katja Pahkala","doi":"10.1016/j.atherosclerosis.2025.120595","DOIUrl":"10.1016/j.atherosclerosis.2025.120595","url":null,"abstract":"<div><h3>Backgroung and aims</h3><div>Inflammation is associated with cardiovascular disease development and microvascular dysfunction. The aim of the present study is to test the hypothesis that long-term exposure to chronic inflammation in childhood and adulthood is associated with adverse retinal microvascular structure in young and mid-adulthood.</div></div><div><h3>Methods</h3><div>We analyzed data derived from the Special Turku Coronary Risk Factor Intervention Project (STRIP) and longitudinal Cardiovascular Risk in Young Finns Study (YFS). In STRIP, fundus photos were taken in young adulthood (aged 26 years), and in YFS in mid-adulthood (aged 34–49 years). Retinal microvascular measures were derived in both cohorts (arteriolar and venular diameters and tortuosity; additionally, fractal dimensions in STRIP). Cumulative exposure as the area under the curve for high-sensitivity <em>C</em>-reactive protein (hsCRP) and glycoprotein acetyls (GlycA), and other conventional cardiovascular risk factors was determined over a 15- and 17-year period in STRIP, and a 10-year period in YFS. Overall, retinal microvascular and cumulative hsCRP and/or GlycA were available for 344 STRIP and 1211 YFS participants, thus forming the cohort of the present study.</div></div><div><h3>Results</h3><div>In both cohorts, cumulative hsCRP was associated with wider venules when adjusted for sex (and age in YFS), and further for related cardiovascular risk factors. In young adulthood (STRIP), higher exposure to cumulative hsCRP was associated with decreased venular tortuosity, whereas in mid-adulthood (YFS), the association was inverse. Cumulative hsCRP was not associated with arteriolar measures whereas cumulative GlycA showed no significant association with any retinal microvascular measures.</div></div><div><h3>Conclusions</h3><div>Long-term cumulative hsCRP exposure was associated with wider venules in young and mid-adulthood, whereas the associations with venular tortuosity were inconsistent. Wider retinal venules might act as a marker for cumulative inflammatory burden.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"412 ","pages":"Article 120595"},"PeriodicalIF":5.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578373","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":"Effect of alirocumab on coronary plaque stratified by atherothrombotic risk","authors":"Yasushi Ueki ,&nbsp;Ryota Kakizaki ,&nbsp;Tatsuhiko Otsuka ,&nbsp;Tadashi Itagaki ,&nbsp;Sylvain Losdat ,&nbsp;Hiroki Shibutani ,&nbsp;Jonas Häner ,&nbsp;Sarah Bär ,&nbsp;Juan F. Iglesias ,&nbsp;Robert-Jan van Geuns ,&nbsp;David Spirk ,&nbsp;Joost Daemen ,&nbsp;Thomas Engstrøm ,&nbsp;Irene Lang ,&nbsp;Konstantinos C. Koskinas ,&nbsp;Lorenz Räber","doi":"10.1016/j.atherosclerosis.2025.120588","DOIUrl":"10.1016/j.atherosclerosis.2025.120588","url":null,"abstract":"<div><h3>Background and aims</h3><div>Previous clinical studies have demonstrated the enhanced cardiovascular benefit of proprotein convertase subtilisin/kexin type 9 inhibition in high-risk patient subsets; however, the mechanisms underlying the greater benefit among patients at high atherothrombotic risk remain largely unknown. We aimed to investigate the effect of alirocumab on coronary plaque regression stratified according to AHA/ACC guideline-defined risk categories among patients with acute myocardial infarction (AMI).</div></div><div><h3>Methods</h3><div>This was a substudy of the PACMAN-AMI trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in addition to high-intensity statin in AMI patients undergoing percutaneous coronary intervention. Patients underwent serial intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT) in the non-infarct-related arteries at baseline and after 52 weeks. Patients were categorized as very-high risk (VHR) if they had at least 1 prior cardiovascular event or at least 2 high-risk conditions. The key outcome measures were percent atheroma volume (PAV) by IVUS, maximum lipid core burden index within 4 mm (maxLCBI_4mm) by NIRS, minimum fibrous cap thickness (FCT) and macrophage angle by OCT.</div></div><div><h3>Results</h3><div>Among 263 patients available for serial IVUS data, 111 (42.2 %) were classified as VHR. A greater reduction in PAV by alirocumab was observed in the non-VHR group compared with the VHR group (difference in change: 1.8 % [-2.5 to −1.0], P &lt; 0.001 vs. −0.8 % [-1.7 to −0.1], P = 0.068, P_{for interaction} = 0.109). Similarly, greater reduction in maxLCBI_4mm and macrophage angle was observed in non-VHR vs. VHR patients (−72.8 [-109.3 to −36.4], P &lt; 0.001 vs. −10.1 [-53.4 to 33.2], P = 0.647, P_{for interaction} = 0.030, and +21.2 μm [-1.4 to +43.8], P = 0.066 vs. +35.0 μm [+8.3 to +61.8], P = 0.011, P_{for interaction} = 0.031, respectively). In contrast, the increase in minimum FCT was more pronounced in the VHR group than the non-VHR group (difference in change: +21.2 μm [-1.4 to +43.8], P = 0.066 vs. +35.0 μm [+8.3 to +61.8], P = 0.011, P_{for interaction} = 0.440).</div></div><div><h3>Conclusions</h3><div>Among AMI patients, the addition of alirocumab to high-intensity statin therapy resulted in greater coronary plaque regression and lipid burden reduction in patients not at VHR. Further investigation is needed to clarify the impact of atherothrombotic risks on plaque regression and subsequent risk reduction in different patient subsets.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"412 ","pages":"Article 120588"},"PeriodicalIF":5.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622638","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":"Post-transcriptional modifications on tRNA fragments confer functional changes to high-density lipoproteins in atherosclerosis","authors":"Elizabeth M. Semler ,&nbsp;Danielle L. Michell ,&nbsp;Philip J. Kingsley ,&nbsp;Marisol A. Ramirez ,&nbsp;Clark Massick ,&nbsp;Mark Castleberry ,&nbsp;Amanda C. Doran ,&nbsp;John J. Carr ,&nbsp;Lawrence Marnett ,&nbsp;Quanhu Sheng ,&nbsp;MacRae F. Linton ,&nbsp;Kasey C. Vickers","doi":"10.1016/j.atherosclerosis.2025.120584","DOIUrl":"10.1016/j.atherosclerosis.2025.120584","url":null,"abstract":"<div><h3>Background and aims</h3><div>Epitranscriptomic RNA modifications play a crucial role in RNA processing, stability, and function. Small non-coding RNAs (sRNAs), such as tRNA-derived fragments (tDRs), likely inherit modifications from parent transcripts. Evidence supports that cell-free sRNA modifications regulate gene expression, modulate immune responses, and are closely linked to the pathogenesis of immune related diseases. Given that high-density lipoproteins (HDL) transport sRNAs from parent transcripts with extensive modifications, we predicted that many HDL-sRNAs harbor immune regulatory modifications that contribute to HDL functionality.</div></div><div><h3>Methods</h3><div>To assess HDL-sRNA modifications in atherosclerotic cardiovascular disease (ASCVD), total RNAs were isolated from HDL of healthy subjects and those with advanced ASCVD. HDL-sRNA modifications were quantified using liquid chromatography-tandem mass-spectrometry (LC-MS/MS), AlkB-facilitated RNA (de)Methylation Sequencing (ARM-seq), and qPCR.</div></div><div><h3>Results</h3><div>LC-MS/MS revealed a significant increase in the relative levels of modified nucleosides on HDL in ASCVD and healthy individuals. ARM-seq identified candidate tDR-ArgACG fragments harboring 1-methyladenosine (m¹A) modifications that were enriched in ASCVD subjects compared to controls. Bulk mRNA sequencing showed significant macrophage gene expression changes in response to ASCVD-HDL-sRNA uptake, including <em>TMEM123</em>, a transmembrane protein linked to immune cell migration and adhesion. Reconstituted HDL loaded with m¹A-tDR-ArgACG were also found to significantly increase <em>TMEM123</em> expression in primary macrophages, and blocking m¹A using an anti-m¹A neutralizing antibody attenuated this effect.</div></div><div><h3>Conclusions</h3><div>Results support a model in which HDL-delivered m¹A-HDL-tDRs regulate immune signaling, macrophage activation, and pro-inflammatory sub-phenotypes within the atherosclerotic lesion.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"412 ","pages":"Article 120584"},"PeriodicalIF":5.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733055","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":"OGT deficiency in vascular smooth muscle orchestrates foam cell formation and PANoptosis during atherosclerotic progression","authors":"Boao Liu ,&nbsp;Huiping Ma ,&nbsp;Yunxuan Guo ,&nbsp;Hao Luo ,&nbsp;Jie Ma ,&nbsp;Shengqi Fu ,&nbsp;Lin Xu ,&nbsp;Xiwen Xiong","doi":"10.1016/j.atherosclerosis.2025.120604","DOIUrl":"10.1016/j.atherosclerosis.2025.120604","url":null,"abstract":"<div><h3>Background and aims</h3><div>Vascular smooth muscle cells (VSMCs) contribute to atherosclerotic foam cell formation, but mechanisms regulating their phenotypic switching and programmed cell death remain unclear. O-GlcNAcylation, a nutrient-sensitive post-translational modification implicated in vascular calcification, lacks defined roles in VSMC foam cell biology.</div></div><div><h3>Methods</h3><div>Inducible smooth muscle-specific <em>Ogt</em> knockout mice on an <em>Apoe</em>^{<em>−/−</em>} background were subjected to streptozotocin-induced hyperglycemia and a 12-week high-fat/high-cholesterol diet. Immunostaining of aortic sections was performed to evaluate the expression and localization of OGT, O-GlcNAc, and α-SMA in VSMCs and their derived foam cells. Primary VSMCs were treated with oxidized LDL to induce foam cell formation, and OGT inhibition was achieved either pharmacologically using OSMI-1 or genetically via shOgt adenovirus infection. Lipid accumulation was assessed by BODIPY/Oil Red O staining, and cell death was evaluated via TUNEL assay, flow cytometry, and Western blot.</div></div><div><h3>Results</h3><div>OGT expression and global O-GlcNAcylation were reduced in VSMCs during atherogenic progression. <em>Ogt</em> deletion in VSMCs promoted foam cell formation with enhanced lipid accumulation but paradoxically reduced atherosclerotic lesion area concurrent with increased intraplaque cell death. Both genetic and pharmacological OGT inhibition recapitulated this duality in vitro, simultaneously accelerating lipid accumulation while triggering PANoptosis, as evidenced by concurrent activation of cleaved caspase-3, phosphorylated MLKL, and cleaved GSDMD. Individual inhibition of apoptosis, necroptosis, or pyroptosis provided only partial rescue.</div></div><div><h3>Conclusions</h3><div>OGT acts as a dual regulator of VSMC fate, attenuating plaque burden through PANoptosis induction while promoting foam cell formation, revealing its complex role in atherosclerosis pathogenesis and suggesting context-dependent therapeutic implications.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"412 ","pages":"Article 120604"},"PeriodicalIF":5.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622528","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 between C-reactive protein and adverse events in secondary cardiovascular prevention: A systematic review and meta-analysis of prognostic factor studies","authors":"Raffaele Piccolo ,&nbsp;Angelo Laino ,&nbsp;Antonio Pio Vitale ,&nbsp;Anna Franzone ,&nbsp;Daniele Giacoppo ,&nbsp;Eduardo Bossone ,&nbsp;Davide Capodanno ,&nbsp;Giovanni Esposito","doi":"10.1016/j.atherosclerosis.2025.120574","DOIUrl":"10.1016/j.atherosclerosis.2025.120574","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background and aims&lt;/h3&gt;&lt;div&gt;C-reactive protein (CRP) has been associated with an increased risk of cardiovascular events in the setting of primary prevention; however, its risk association in secondary cardiovascular prevention remains unclear. We evaluated the prognostic role of CRP across the spectrum of patients with established atherosclerotic cardiovascular disease (ASCVD).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We performed a systematic review and meta-analysis by screening Embase and MEDLINE databases from inception through November 2024. We included studies reporting adjusted risk associations between CRP and cardiovascular events among patients with ASCVD. Two reviewers extracted data and assessed the risk of bias. Data were extracted using an adaption of the Checklist for Critical Appraisal and Data Extraction for Systematic Review of Prediction Modelling Studies (CHARMS-PF). The primary analysis was conducted using a random-effects model within a Bayesian framework. Risk of bias was assessed using the Quality in Prognosis Studies tool. The GRADE (grading of recommendations assessment, development, and evaluation) approach was used to rate the certainty in the prognostic yield of CRP. The principal outcome was major adverse cardiovascular events. Additional outcomes included: all-cause death, myocardial infarction, cardiovascular death, and cerebrovascular events.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We included 27 studies, published from 2002 to 2024, and involving 193,761 participants (65,204 or 34 % females). Higher CRP levels were defined accordingly to the included studies and ranged from 0.5 to 5.0 mg/L 26 studies adjusted for conventional cardiovascular risk factors (age, sex, smoking, diabetes, dyslipidemia, hypertension); one omitted smoking status but included the others. Higher CRP levels were associated with an increased risk of major adverse cardiovascular events (adjusted hazard ratio, aHR, 1.55, 95 % credible intervals, CrI, 1.39 to 1.73; tau = 0.24, 95 %CrI 0.14 to 0.34; high certainty), all-cause death (aHR 1.92, 95 %CrI 1.52 to 2.41; tau = 0.30, 95 %CrI 0.14 to 0.51; moderate certainty), myocardial infarction (aHR 1.40, 95 %CrI 1.22 to 1.63; tau = 0.066, 95 %CrI 0.001 to 0.28; moderate certainty), and cardiovascular death (aHR 1.35, 95 %CrI 0.98 to 1.84; tau = 0.20, 95 %CrI 0.001 to 0.54; low certainty) after adjustment for traditional risk factors. The association between CRP and the risk of cerebrovascular events was inconclusive (aHR 1.52, 95 %CrI 0.69 to 3.32; tau = 0.33 95 %CrI 0.001 to 0.85; very low certainty). Dose-response Bayesian meta-analysis showed a non-linear association between CRP and major cardiovascular events, with levels between 2 and 4 mg/L being associated with clinically relevant higher risk. A similar dose-response relationship was observed also for all-cause death.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Among patients with ASCVD, elevated levels of CRP are associated with an increase","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"412 ","pages":"Article 120574"},"PeriodicalIF":5.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761933","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":"Remnant cholesterol and particle number of VLDL subfractions in coronary artery disease: Pros and cons","authors":"Mia Ø. Johansen ,&nbsp;Signe Vedel-Krogh ,&nbsp;Sune F. Nielsen ,&nbsp;Shoaib Afzal ,&nbsp;George Davey Smith ,&nbsp;Børge G. Nordestgaard","doi":"10.1016/j.atherosclerosis.2025.120605","DOIUrl":"10.1016/j.atherosclerosis.2025.120605","url":null,"abstract":"<div><div>Emerging evidence from large observational studies and causal genetic studies suggest that elevated very-low-density lipoproteins (VLDL) are important and independent risk factors for atherosclerosis, myocardial infarction, and coronary artery disease. The cholesterol content of VLDL particles is often combined as overall remnant cholesterol; however, VLDL particles encompasses a heterogeneous group of lipoproteins that vary significantly in size, density, and structural composition, contributing to metabolic heterogeneity of VLDL particles. This heterogeneity has been suggested important for understanding the atherogenicity of VLDL particles. Nevertheless, remnant cholesterol lack precision to capture metabolic heterogeneity of VLDL subfractions; in contrast, advanced techniques such as nuclear magnetic resonance (NMR) spectroscopy provide more accurate estimates of VLDL particle number and cholesterol content across subfractions. This review aims at summarizing current evidence of the association between remnant cholesterol and particle number of VLDL subfractions as risk factors for myocardial infarction and coronary artery disease including pros and cons for using easily accessible remnant cholesterol versus using more advanced measurement methods for estimation of particle number of VLDL subfractions.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"412 ","pages":"Article 120605"},"PeriodicalIF":5.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653297","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}