Atherosclerosis最新文献

{"title":"Single bolus PCSK9 Inhibition: A new approach to plaque stabilisation","authors":"Stephen J. Nicholls, Gavin PR. Manmathan","doi":"10.1016/j.atherosclerosis.2024.118628","DOIUrl":"10.1016/j.atherosclerosis.2024.118628","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118628"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493739","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":"Incremental prognostic value of pericoronary adipose tissue attenuation beyond conventional features in patients with nonobstructive coronary artery disease.","authors":"Nan Zheng, Zinuan Liu, Yipu Ding, Xi Wang, Jing Li, Guanhua Dou, Ran Xin, Ziqiang Guo, Guanxi Chen, Jing Jing, Bai He, Dongkai Shan, Junjie Yang","doi":"10.1016/j.atherosclerosis.2024.119075","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119075","url":null,"abstract":"<p><strong>Background and aims: </strong>It remains uncertain whether pericoronary adipose tissue attenuation (PCATa) is associated with clinical outcome in patients with nonobstructive coronary artery disease (CAD). We aim to investigate the incremental prognostic value of PCATa beyond clinical and coronary computed tomographic angiography (CCTA) features in patients with nonobstructive CAD.</p><p><strong>Methods: </strong>Consecutive patients with chest pain suspected of CAD referred for CCTA from January 2017 to December 2018 were prospectively included. Multivariable Cox proportional hazard regression analysis was employed to identify the predictive factors for major adverse cardiovascular events (MACE), while the receiver operating characteristics (ROC) curve was utilized to assess the discriminatory capacity of PCATa. Kaplan-Meier curves were ultilized to visually represent event-free survival and were compared using Log-rank tests among groups stratified by high-risk plaque (HRP) and PCATa.</p><p><strong>Results: </strong>Of the 1614 patients (mean age 59.0 years, 55.6 % male) with nonobstructive CAD, 68 (4.2 %) suffered MACE during a median follow-up of 28.6 months. After multivariable adjustment, PCATa was identified as an independent predictor (HR: 1.060, 95%CI: 1.025-1.096, p = 0.001). The inclusion of PCATa significantly enhanced the discrimination capacity [AUC:0.72 (0.66-0.78), p = 0.041] and risk reclassification (NRI = 1.99, p < 0.001; IDI = 0.93, p < 0.001) beyond the influence of clinical and CCTA factors. In the presence of HRP, a higher PCATa was found to be associated with a relatively higher risk of MACE compared to a lower PCATa (HR: 2.45, 95%CI: 1.09-5.52, p = 0.031).</p><p><strong>Conclusions: </strong>PCATa is positively correlated with adverse outcome in patients with nonobstructive CAD, and it offers incremental predictive value beyond clinical variables and CCTA characteristics.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119075"},"PeriodicalIF":4.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794302","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":"Oral microbiome alpha diversity and all-cause, cardiovascular, and non-cardiovascular mortality in US adults: Evidence from the NHANES 2009-2019.","authors":"Rajib Mondal, Rani Baroi Ritu, Kaori Kitaoka, Nazar Mohd Azahar, Mohammad Moniruzzaman, Soshiro Ogata, Eri Kiyoshige, Haruka Tohara, Yusuke Kobayashi, Naoki Kashihara, Toshio Naito, Naoki Nakashima, Kosuke Tamura, Kunihiro Nishimura, Anthony J Viera, Yuichiro Yano","doi":"10.1016/j.atherosclerosis.2024.119074","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119074","url":null,"abstract":"<p><strong>Background and aims: </strong>Knowledge about the association between oral microbiome diversity within individuals and cardiovascular disease (CVD) and non-CVD mortality is scarce. Besides, variation by sex and racial and ethnic groups, and the potential mediators of these associations remain unclear. We aimed to investigate the associations of oral microbiome alpha diversity with all-cause, CVD, and non-CVD mortality, and the interaction effects of sex and racial and ethnic groups and potential mediators in the associations.</p><p><strong>Methods: </strong>The National Health and Nutrition Examination Survey (NHANES) is a population-based observational study, conducted periodically in Mexican American, Other Hispanic, Non-Hispanic (NH) White, NH Black, and other racial/ethnic participants. We linked 2009-12 survey data of 8199 adults to the mortality data until 2019. By analyzing RNA gene sequences from oral rinse samples, microbiome alpha diversity within individuals was assessed using operational taxonomic unit (OTU) richness. Potential mediators included obesity, diabetes mellitus, dyslipidemia, hypertension, and periodontitis. Multivariable Cox proportional hazards regression and causal mediation analysis were used.</p><p><strong>Results: </strong>Baseline mean ± standard deviation (SD) age was 42.1 ± 15.1 years. Over a median follow-up of 9.1 years, 405 all-cause mortality occurred (CVD, 105; non-CVD, 300). Each 1-SD increment in OTU richness was inversely associated with all-cause mortality (hazard ratio [HR] 0.92, 95 % confidence interval [CI] 0.90-0.95), CVD mortality (HR, 0.92; 95 % CI, 0.90-0.95), and non-CVD mortality (HR, 0.92; 95 % CI, 0.90-0.95). With evidence of significant racial and ethnic groups-interaction (p <0.05), these associations were evident in Mexican American, NH White, and others racial/ethnic participants. None of the potential mediators significantly mediated the associations of OTU richness with all-cause, CVD, and non-CVD mortality.</p><p><strong>Conclusions: </strong>Lower oral microbiome alpha diversity is associated with higher risk for all-cause, CVD, and non-CVD mortality, and the associations are varied by racial and ethnic groups.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"119074"},"PeriodicalIF":4.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791022","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":"Circulatory miRNAs in essential hypertension.","authors":"Daria Kostiniuk, Saara Marttila, Emma Raitoharju","doi":"10.1016/j.atherosclerosis.2024.119069","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119069","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are short non-coding RNAs, that regulate gene-expression at post-transcriptional level. Unlike other RNA species, blood miRNAs circulate in a highly stable form, either within extracellular vesicles or bound to proteins. In recent years, circulatory miRNA profiles have been proposed as potential biomarkers for multitude of pathologies, including essential hypertension. However, the evidence of miRNA biomarker potential is limited, mainly due to the scarcity of profiling studies associating miRNA levels with hypertension. Furthermore, most of these studies have been performed with preselected miRNA pool, limiting their discovery potential. Here, we summarize the results of the unbiased profiling studies and additionally discuss findings from targeted miRNA analysis. Only miR-30e has been found to be associated with hypertension in more than one unbiased study. The targeted analyses highlight the association of miR-1, -21, -34a, -92a, -122, -126, -143, -145, -605, -623, -1299, as well as let-7 and miR-30 families with hypertension. Current literature indicates that some of these miRNAs are involved in hypertension-associated vascular dysfunction and the development of atherosclerosis, suggesting a novel mechanism for cardiovascular disease risk posed by hypertension. All in all, studies associating hypertension with circulatory miRNA profiles are scarce, with several limitations affecting the comparability of the studies. This review discusses the functions and potential mechanisms linking the identified miRNAs to hypertension and underscores the need for further research.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119069"},"PeriodicalIF":4.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791018","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":"De novo lipid synthesis in cardiovascular tissue and disease","authors":"Tariq J. Khan ,&nbsp;Clay F. Semenkovich ,&nbsp;Mohamed A. Zayed","doi":"10.1016/j.atherosclerosis.2024.119066","DOIUrl":"10.1016/j.atherosclerosis.2024.119066","url":null,"abstract":"<div><div>Most tissues have the capacity for endogenous lipid synthesis. A crucial foundational pathway for lipid synthesis is <em>de novo</em> lipid synthesis (DNL), a ubiquitous and complex metabolic process that occurs at high levels in the liver, adipose and brain tissue. Under normal physiological conditions, DNL is vital in converting excess carbohydrates into fatty acids. DNL is linked to other pathways, including the endogenous synthesis of phospholipids and sphingolipids. However, abnormal lipid synthesis can contribute to various pathologies and clinical conditions. Experimental studies involving dietary restriction and <em>in vivo</em> genetic modifications provide compelling evidence demonstrating the significance of lipid synthesis in maintaining normal cardiovascular tissue function. Similarly, clinical investigations suggest altered lipid synthesis can harm cardiac and arterial tissues, thereby influencing cardiovascular disease (CVD) development and progression. Consequently, there is increased interest in exploring pharmacological interventions that target lipid synthesis metabolic pathways as potential strategies to alleviate CVD. Here we review the physiological and pathological impact of endogenous lipid synthesis and its implications for CVD. Since lipid synthesis can be targeted pharmacologically, enhancing our understanding of the molecular and biochemical mechanisms underlying lipid generation and cardiovascular function may prompt new insights into CVD and its treatment.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"400 ","pages":"Article 119066"},"PeriodicalIF":4.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142744649","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":"Interaction between chronic kidney disease and atrial fibrillation on incident stroke and all-cause mortality: Matched cohort study of 49,594 patients.","authors":"David Ray Chang, Hsiu-Yin Chiang, Ya-Luan Hsiao, Uyen-Minh Le, Yu-Cuyan Hong, Shih-Sheng Chang, Ke-Wei Chen, Che-Chen Lin, Hung-Chieh Yeh, I-Wen Ting, Pei-Chun Chen, Hung-Lin Chen, Kuan-Cheng Chang, Chin-Chi Kuo","doi":"10.1016/j.atherosclerosis.2024.119055","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119055","url":null,"abstract":"<p><strong>Background and aims: </strong>The interaction between full-spectrum chronic kidney disease (CKD) and atrial fibrillation (AF) on ischemic stroke and all-cause mortality risk, particularly in stage 4 and 5 CKD, remains undetermined.</p><p><strong>Methods: </strong>This matched cohort study identified incident AF patients using the International Classification of Disease codes and electrocardiograms from the Clinical Research Data Repository of China Medical University Hospital between 2003 and 2020. For each AF patient, we selected four controls without AF and matched them by age, sex, eGFR within 10 mL/min/1.73 m², end-stage kidney disease (ESKD) vintage, and diagnosis year. Multivariable Cox proportional hazard models were utilized to assess the interaction between AF and CKD on three-year ischemic stroke and all-cause mortality outcomes.</p><p><strong>Results: </strong>Within a total of 10,155 patients and 39,439 controls, incidence rates were 3.03 % and 1.48 % for ischemic stroke and 15.6 % and 9.53 % for overall mortality, respectively. In AF, the stroke risk was the highest among patients with stage 4 and 5-ND (non-dialysis) CKD with adjusted hazard ratio (aHR) of 3.31 (95 % CI, 2.46-4.45) and 2.73 (1.88-3.96), respectively. The mortality risk difference varied between 45% and 177 % with the highest difference noted in ESKD (aHR 3.36 [95 % CI, 2.84-3.98] in AF vs. 1.59 [95 % CI, 1.28-1.96] in non-AF; interaction p < 0.001). Anticoagulation therapy significantly lowered the mortality risk among patients with AF and advanced CKD (3-way interaction p < 0.001).</p><p><strong>Conclusions: </strong>The risk of ischemic stroke and overall mortality was particularly high among patients with concurrent AF and stage 4 and 5-ND CKD, underscoring the urgent evidence to optimize prognosis.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"401 ","pages":"119055"},"PeriodicalIF":4.9,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794304","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":"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":"Remnant cholesterol and long-term incidence of death in coronary artery disease patients.","authors":"Heinz Drexel, Arthur Mader, Barbara Larcher, Andreas Festa, Alexander Vonbank, Peter Fraunberger, Andreas Leiherer, Christoph H Saely","doi":"10.1016/j.atherosclerosis.2024.119048","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119048","url":null,"abstract":"<p><strong>Background: </strong>Remnant cholesterol (RC), defined as non-HDL-non-LDL cholesterol, has attracted recent scientific interest as a candidate lipid factor for residual cardiovascular risk. Despite a rising amount of epidemiologic information, there are imprecisions because most available data arise from non-fasting, frozen and calculated values.</p><p><strong>Methods: </strong>We enrolled 1474 consecutive patients with angiographically proven CAD, and measured RC in strictly fasting, non-frozen samples with a direct assay for LDL-C. Prospectively, all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE) were recorded over a mean follow-up period of 11.6 ± 5.0 years, covering 17098 patient years.</p><p><strong>Results: </strong>During follow-up, CAD patients had a rate of all-cause mortality of 52.2 % (n = 769), of cardiovascular mortality of 20.6 % (n = 303), and an incidence of major adverse cardiovascular events (MACE) of 39.1 % (n = 576). Prospectively, RC was associated with all-cause mortality (HR 1.12 [1.03-1.23], p = 0.009), cardiovascular mortality (HR 1.20 [1.06-1.36], p = 0.005), and MACE (HR 1.10 [1.01-1.21], p = 0.033) in Cox regression analyses across various levels of adjustment (age, sex, smoking, LDL-C, HDL-C, hypertension, T2DM, and BMI). Findings did not differ between women and men. Furthermore, there was no discernible influence of statin treatment.</p><p><strong>Conclusions: </strong>From our data we conclude that RC is associated with future all-cause mortality, cardiovascular mortality and MACE in patients with established coronary artery disease. Proper pre-analytic and analytic methods provided, RC represents a reliable indicator of residual risk.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119048"},"PeriodicalIF":4.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779182","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}