From Genetic Findings to new Intestinal Molecular Targets in Lipid Metabolism.

IF 5.7 2区医学 Q1 PERIPHERAL VASCULAR DISEASE

Current Atherosclerosis Reports Pub Date : 2025-01-11 DOI:10.1007/s11883-024-01264-w

Cédric Le May, Simon Ducheix, Bertrand Cariou, Antoine Rimbert

{"title":"From Genetic Findings to new Intestinal Molecular Targets in Lipid Metabolism.","authors":"Cédric Le May, Simon Ducheix, Bertrand Cariou, Antoine Rimbert","doi":"10.1007/s11883-024-01264-w","DOIUrl":null,"url":null,"abstract":"Purpose of review: While lipid-lowering therapies demonstrate efficacy, many patients still contend with significant residual risk of atherosclerotic cardiovascular diseases (ASCVD). The intestine plays a pivotal role in regulating circulating lipoproteins levels, thereby exerting influence on ASCVD pathogenesis. This review underscores recent genetic findings from the last six years that delineate new biological pathways and actors in the intestine which regulate lipid-related ASCVD risk.Recent findings: Specifically, we detail the role of LIMA1 in cholesterol absorption within enterocytes, the function of PLA2G12B in the expansion and lipidation of chylomicrons, the involvement of SURF4 in lipoprotein secretion, and the discovery of a gut-derived hormone named CHOLESIN that modulates cholesterol homeostasis through GPR146 via a gut-liver crosstalk. We further discuss the potential of these newly identified genes and pathways as novel targets for pharmaceutical intervention. Newly identified genetic and intestinal molecular mechanisms offer promising opportunities for preventing and treating ASCVD, but careful evaluation and further research are needed to optimize their clinical application.","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":"27 1","pages":"26"},"PeriodicalIF":5.7000,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Atherosclerosis Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11883-024-01264-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose of review: While lipid-lowering therapies demonstrate efficacy, many patients still contend with significant residual risk of atherosclerotic cardiovascular diseases (ASCVD). The intestine plays a pivotal role in regulating circulating lipoproteins levels, thereby exerting influence on ASCVD pathogenesis. This review underscores recent genetic findings from the last six years that delineate new biological pathways and actors in the intestine which regulate lipid-related ASCVD risk.

Recent findings: Specifically, we detail the role of LIMA1 in cholesterol absorption within enterocytes, the function of PLA2G12B in the expansion and lipidation of chylomicrons, the involvement of SURF4 in lipoprotein secretion, and the discovery of a gut-derived hormone named CHOLESIN that modulates cholesterol homeostasis through GPR146 via a gut-liver crosstalk. We further discuss the potential of these newly identified genes and pathways as novel targets for pharmaceutical intervention. Newly identified genetic and intestinal molecular mechanisms offer promising opportunities for preventing and treating ASCVD, but careful evaluation and further research are needed to optimize their clinical application.

查看原文本刊更多论文

从遗传学发现到脂质代谢的肠道新分子靶点。

综述目的：虽然降脂疗法显示出疗效，但许多患者仍然存在显著的动脉粥样硬化性心血管疾病（ASCVD）残留风险。肠道在调节循环脂蛋白水平中起关键作用，从而影响ASCVD的发病机制。这篇综述强调了最近六年的遗传学发现，这些发现描绘了肠道中调节脂质相关ASCVD风险的新生物学途径和参与者。最近的研究发现：具体来说，我们详细介绍了LIMA1在肠细胞内胆固醇吸收中的作用，PLA2G12B在乳糜微粒扩张和脂化中的功能，SURF4在脂蛋白分泌中的作用，以及一种名为CHOLESIN的肠道源性激素的发现，该激素通过GPR146通过肠-肝串音调节胆固醇稳态。我们进一步讨论了这些新发现的基因和途径作为药物干预的新靶点的潜力。新发现的遗传和肠道分子机制为预防和治疗ASCVD提供了有希望的机会，但需要仔细评估和进一步研究以优化其临床应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Current Atherosclerosis Reports 医学-

CiteScore

9.00

自引率

3.40%

发文量

审稿时长

6-12 weeks

期刊介绍： The aim of this journal is to systematically provide expert views on current basic science and clinical advances in the field of atherosclerosis and highlight the most important developments likely to transform the field of cardiovascular prevention, diagnosis, and treatment. We accomplish this aim by appointing major authorities to serve as Section Editors who select leading experts from around the world to provide definitive reviews on key topics and papers published in the past year. We also provide supplementary reviews and commentaries from well-known figures in the field. An Editorial Board of internationally diverse members suggests topics of special interest to their country/region and ensures that topics are current and include emerging research.