Atherosclerosis最新文献

{"title":"Prevalence, genetic variants, and clinical implications of hypocholesterolemia in children","authors":"Urh Groselj ,&nbsp;Jan Kafol ,&nbsp;Neza Molk ,&nbsp;Katarina Sedej ,&nbsp;Matej Mlinaric ,&nbsp;Jaka Sikonja ,&nbsp;Ursa Sustar ,&nbsp;Barbara Cugalj Kern ,&nbsp;Jernej Kovac ,&nbsp;Tadej Battelino ,&nbsp;Marusa Debeljak","doi":"10.1016/j.atherosclerosis.2024.119065","DOIUrl":"10.1016/j.atherosclerosis.2024.119065","url":null,"abstract":"<div><h3>Background and aims</h3><div>In contrast to extensively studied hypercholesterolemia, knowledge of hypocholesterolemia is limited. This study aims to assess the prevalence, clinical characteristics, and genetics of children and adolescents with hypocholesterolemia.</div></div><div><h3>Methods</h3><div>This national prospective cross-sectional cohort study was part of Slovenia's universal opt-out cholesterol screening program. The first part assessed hypocholesterolemia prevalence among 3538 children aged 5 years, randomly selected at the mandatory check-up. The second part included analysis of demographic and clinical data and genetic testing of 71 individuals with suspected hypocholesterolemia (total cholesterol [TC] &lt; 3.0 mmol/L [116.0 mg/dL]) referred to the Lipid Clinic of University Children's Hospital Ljubljana.</div></div><div><h3>Results</h3><div>The prevalence of hypocholesterolemia among 3538 children was 2.66 % (95 % CI: 2.13–3.19 %). Among the 71 genetically tested individuals with suspected hypocholesterolemia, those with pathogenic variants had lower TC (2.58 ± 0.44 mmol/L vs. 2.85 ± 0.42 mmol/L [99.77 ± 17.02 mg/dL vs. 110.20 ± 16.24 mg/dL]; <em>p</em> = 0.037) and low-density lipoprotein cholesterol (1.00 ± 0.40 mmol/L vs. 1.33 ± 0.40 mmol/L [38.67 ± 15.47 mg/dL vs. 51.43 ± 15.47 mg/dL]; <em>p</em> = 0.014) compared to those without such variants. Genetic testing identified pathogenic alterations in 15 subjects, including 4 novel loss-of-function variants in the APOB gene. All but one subject were asymptomatic.</div></div><div><h3>Conclusions</h3><div>This study provides new clinical and genetic insights into hypocholesterolemia. Asymptomatic patients with hypocholesterolemia may not require further evaluation, but additional research is needed to understand hypocholesterolemia better.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"400 ","pages":"Article 119065"},"PeriodicalIF":4.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver metabolism in human MASLD: A review of recent advancements using human tissue metabolomics","authors":"Emily Flam,&nbsp;Joel T. Haas,&nbsp;Bart Staels","doi":"10.1016/j.atherosclerosis.2024.119054","DOIUrl":"10.1016/j.atherosclerosis.2024.119054","url":null,"abstract":"<div><div>Global incidence of Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is on the rise while treatments remain elusive. MASLD is a disease of dysregulated systemic and hepatic metabolism. Current understanding of disease pathophysiology as it relates to metabolome changes largely comes from studies on animal models and human plasma. However, human tissue data are crucial for transitioning from mechanisms to clinical therapies. The close relationship between MASLD and comorbidities like obesity, type 2 diabetes and dyslipidemia make it difficult to determine the contribution from liver disease itself. Here, we review recent metabolomics studies in liver tissue from human MASLD patients, which have predominately focused on lipid metabolism, but also include bile acid, tricarboxylic acid (TCA) cycle, and branched chain amino acid (BCAA) metabolism. Several clinical trials are underway to target various of these lipid-related pathways in MASLD. Although only the β-selective thyroid hormone receptor agonist resmetirom has so far been approved for use, many metabolism-targeting pharmaceuticals show promising results for halting disease progression, if not promoting outright reversal. Ultimately, the scarcity of human tissue data and the variability of confounding factors, like obesity, within and between cohorts are impediments to the pathophysiological understanding required for efficient development of metabolic treatments.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"400 ","pages":"Article 119054"},"PeriodicalIF":4.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699285","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":"Lipotoxicity-driven metabolic dysfunction-associated steatotic liver disease (MASLD)","authors":"Santiago Iturbe-Rey ,&nbsp;Claudia Maccali ,&nbsp;Marco Arrese ,&nbsp;Patricia Aspichueta ,&nbsp;Claudia P. Oliveira ,&nbsp;Rui E. Castro ,&nbsp;Ainhoa Lapitz ,&nbsp;Laura Izquierdo-Sanchez ,&nbsp;Luis Bujanda ,&nbsp;Maria J. Perugorria ,&nbsp;Jesus M. Banales ,&nbsp;Pedro M. Rodrigues","doi":"10.1016/j.atherosclerosis.2024.119053","DOIUrl":"10.1016/j.atherosclerosis.2024.119053","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of liver lesions, ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), that may further progress to cirrhosis. MASLD is estimated to affect more than one third of the general population and it represents a risk factor for end-stage liver failure and liver cancer, substantially contributing to liver-related morbidity and mortality. Although the pathogenesis of MASLD is incompletely understood, it is known to consist of a multifactorial process influenced by extrinsic and intrinsic factors such as metabolic, environmental and demographic features, gut microbiota and genetics. Dysregulation of both extracellular and intracellular lipid composition is known to promote the generation of toxic lipid species, thereby triggering lipotoxicity and cellular stress. These events ultimately lead to the activation of distinct cell death pathways, resulting in inflammation, fibrogenesis and, eventually, carcinogenesis. In this manuscript, we provide a comprehensive review of the role of lipotoxicity during MASLD pathogenesis, discussing the most relevant lipid species and related molecular mechanisms, summarizing the cell type-specific effects and highlighting the most promising putative therapeutic strategies for modulating lipotoxicity and lipid metabolism in MASLD.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"400 ","pages":"Article 119053"},"PeriodicalIF":4.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statin-associated muscle symptoms: Not simply a genetic predisposition.","authors":"Nicola Ferri, Alberto Corsini","doi":"10.1016/j.atherosclerosis.2024.119047","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119047","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119047"},"PeriodicalIF":4.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643751","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":"HDL and cardiovascular risk.","authors":"Manuel Jesús Romero-Jiménez","doi":"10.1016/j.atherosclerosis.2024.119050","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119050","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119050"},"PeriodicalIF":4.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646513","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":"Arterial calcification volume is associated with a higher risk of cardiovascular events in pseudoxanthoma elasticum","authors":"Iris M. Harmsen ,&nbsp;Frank L.J. Visseren ,&nbsp;Madeleine Kok ,&nbsp;Pim A. de Jong ,&nbsp;Wilko Spiering","doi":"10.1016/j.atherosclerosis.2024.119051","DOIUrl":"10.1016/j.atherosclerosis.2024.119051","url":null,"abstract":"<div><h3>Background and aims</h3><div>Pseudoxanthoma elasticum (PXE) patients have more arterial calcification due to lower levels of inorganic pyrophosphate, caused by mutations in the <em>ABCC6</em> gene, but the relation with vascular complications is poorly understood. Because of the slow progressing nature of arterial disease in PXE patients, there is a need for a valid and reliable intermediate endpoint to be used in future clinical trials. Arterial calcification measured on computed tomography (CT) is a promising candidate, if associated with future cardiovascular events. We aimed to establish the relation between arterial calcification measured on CT and future cardiovascular events in patients with PXE.</div></div><div><h3>Methods</h3><div>In this prospective cohort study, patients with PXE from the Dutch UMC Utrecht Expertise Center for PXE (UECP) were included. Arterial calcification volume was measured on low dose full body CT scans. Patient were followed for incident cardiovascular events. The relation between arterial calcification and the risk of cardiovascular events was analyzed using Cox proportional hazard models.</div></div><div><h3>Results</h3><div>In 326 patients (median follow-up 6.0, IQR 3.8–8.2 years) 41 cardiovascular events were observed (21 events per 1000 person years). In patients with no cardiovascular history, there was a significant relation between the log arterial calcification volume at baseline and future cardiovascular events (adjusted HR: 1.87, 95 % CI: 1.14–3.09, per 1 log unit increase in arterial calcification). There was no relation in patients with clinical manifest cardiovascular disease at baseline between arterial calcification volume and future cardiovascular events.</div></div><div><h3>Conclusions</h3><div>Higher arterial calcification volumes on CT in PXE patients are associated with a higher risk of a first cardiovascular event. This cohort study suggests that arterial calcification can be used as an intermediate endpoint in studies evaluating interventions to lower the risk of cardiovascular events.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"400 ","pages":"Article 119051"},"PeriodicalIF":4.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular peroxiredoxin 5 exacerbates atherosclerosis via the TLR4/MyD88 pathway","authors":"Hyae Yon Kweon ,&nbsp;Eun Ju Song ,&nbsp;Se-Jin Jeong ,&nbsp;SoonHo Lee ,&nbsp;Seong-Keun Sonn ,&nbsp;Seungwoon Seo ,&nbsp;Jing Jin ,&nbsp;Sinai Kim ,&nbsp;Tae Kyeong Kim ,&nbsp;Shin Hye Moon ,&nbsp;Doyeon Kim ,&nbsp;Young Mi Park ,&nbsp;Hyun Ae Woo ,&nbsp;Goo Taeg Oh","doi":"10.1016/j.atherosclerosis.2024.119052","DOIUrl":"10.1016/j.atherosclerosis.2024.119052","url":null,"abstract":"<div><h3>Backgroungd and aims</h3><div>Peroxiredoxin 5 (PRDX5), an atypical 2-Cys peroxiredoxin (PRDX), is known to regulate global oxidative stresses and inflammatory responses. Inflammation and oxidative stress are pivotal factors in the development of atherosclerosis, especially in the context of vascular endothelial dysfunction. However, effects of PRDX5 on atherosclerosis remain unclear. This study aimed to elucidate the role of PRDX5 in the pathogenesis of atherosclerosis.</div></div><div><h3>Methods</h3><div>For <em>in vivo</em> analysis, normal chow diet 60-week old Apolipoprotein E knockout (<em>ApoE</em>^{<em>−/−</em>}) and <em>Prdx5</em>^{<em>−/−</em>}<em>; ApoE</em>^{<em>−/−</em>} mice were used for the experiments. For <em>in vitro</em> analysis, human umbilical vein endothelial cells (HUVECs) were stimulated with oxidized LDL (oxLDL; 50 ng/ml) for 24hrs, following serum starvation by incubation with serum-free Endothelial Cell Growth Medium-2 (EGM-2) for 1hr.</div></div><div><h3>Results</h3><div>We observed elevated PRDX5 expression under atherosclerotic conditions in both humans and mice. Unexpectedly, <em>Prdx5</em>^{<em>−/−</em>}<em>; ApoE</em>^{<em>−/−</em>} mice exhibited reduced plaque formation, with no discernible difference in aortic hydrogen peroxide (H₂O₂) levels compared to <em>ApoE</em>^{<em>−/−</em>} mice. Additionally, there was a notable decrease in macrophage accumulation and vascular inflammation in the atherosclerotic aorta of <em>Prdx5</em>^{<em>−/−</em>}<em>; ApoE</em>^{<em>−/−</em>}. <em>In vitro,</em> HUVECs stimulated with oxLDL showed upregulated PRDX5 expression in both lysate and culture medium. Moreover, PRDX5 knockdown in oxLDL-stimulated (oxLDL-siPRDX5) HUVECs significantly reduced the migration and adhesion of human monocytic cells (THP-1) to HUVECs, indicating diminished vascular immune responses. Mechanistically, both <em>in vivo</em> and <em>in vitro</em>, PRDX5 deficiency inhibited the Toll-like receptor 4 (TLR4)/Myeloid differentiation primary response 88 (MyD88) signaling pathway, resulting in reduced nuclear factor kappa B (NF-κB) and P38 phosphorylation. Furthermore, treatment with recombinant PRDX5 (rPRDX5) protein restored TLR4/MyD88 signaling in oxLDL-<em>siPRDX5</em> HUVECs.</div></div><div><h3>Conclusions</h3><div>These data demonstrate that extracellular PRDX5 contributes to endothelial inflammation, promoting macrophage accumulation in the atherosclerotic aorta through activation of TLR4/MyD88/NF-κB and P38 signaling pathways, thereby exacerbating the progression of atherosclerosis.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"400 ","pages":"Article 119052"},"PeriodicalIF":4.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643759","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":"Unveiling feature importance biases in linear regression: Implications for protein-centric cardiovascular research.","authors":"Yoshiyasu Takefuji","doi":"10.1016/j.atherosclerosis.2024.119049","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119049","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119049"},"PeriodicalIF":4.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613875","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":"Reply to: “Correspondence on: “Subclinical atherosclerosis: More data – More insights into prevention” ”","authors":"Heinz Drexel,&nbsp;Andreas Festa","doi":"10.1016/j.atherosclerosis.2024.118634","DOIUrl":"10.1016/j.atherosclerosis.2024.118634","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118634"},"PeriodicalIF":4.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PCSK9 inhibitors in the management of atherosclerotic cardiovascular disease: Current clinical trials and future directions","authors":"Wenyi Nie ,&nbsp;Yingbin Yue ,&nbsp;Jingqing Hu","doi":"10.1016/j.atherosclerosis.2024.119043","DOIUrl":"10.1016/j.atherosclerosis.2024.119043","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 119043"},"PeriodicalIF":4.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613885","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}