Finney Alexandra C, Das Sandeep, Kumar Dhananjay, McKinney M Peyton, Cai Bishuang, Yurdagul Arif, Rom Oren
Department of Pathology and Translational Pathobiology, Louisiana State University Health Shreveport, Shreveport, LA, United States.
Department of Molecular and Cellular Physiology, Louisiana State University Health Shreveport, Shreveport, LA, United States.
Front Cardiovasc Med. 2023 May 2;10:1116861. doi: 10.3389/fcvm.2023.1116861. eCollection 2023.
Therapeutic approaches that lower circulating low-density lipoprotein (LDL)-cholesterol significantly reduced the burden of cardiovascular disease over the last decades. However, the persistent rise in the obesity epidemic is beginning to reverse this decline. Alongside obesity, the incidence of nonalcoholic fatty liver disease (NAFLD) has substantially increased in the last three decades. Currently, approximately one third of world population is affected by NAFLD. Notably, the presence of NAFLD and particularly its more severe form, nonalcoholic steatohepatitis (NASH), serves as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), thus, raising interest in the relationship between these two diseases. Importantly, ASCVD is the major cause of death in patients with NASH independent of traditional risk factors. Nevertheless, the pathophysiology linking NAFLD/NASH with ASCVD remains poorly understood. While dyslipidemia is a common risk factor underlying both diseases, therapies that lower circulating LDL-cholesterol are largely ineffective against NASH. While there are no approved pharmacological therapies for NASH, some of the most advanced drug candidates exacerbate atherogenic dyslipidemia, raising concerns regarding their adverse cardiovascular consequences. In this review, we address current gaps in our understanding of the mechanisms linking NAFLD/NASH and ASCVD, explore strategies to simultaneously model these diseases, evaluate emerging biomarkers that may be useful to diagnose the presence of both diseases, and discuss investigational approaches and ongoing clinical trials that potentially target both diseases.
在过去几十年里，能显著降低循环低密度脂蛋白（LDL）胆固醇水平的治疗方法极大地减轻了心血管疾病的负担。然而，肥胖症流行的持续加剧正开始扭转这一下降趋势。与肥胖症相伴的是，非酒精性脂肪性肝病（NAFLD）的发病率在过去三十年中大幅上升。目前，世界上约三分之一的人口受NAFLD影响。值得注意的是，NAFLD的存在，尤其是其更严重的形式——非酒精性脂肪性肝炎（NASH），是动脉粥样硬化性心血管疾病（ASCVD）的独立危险因素，因此，引发了人们对这两种疾病之间关系的兴趣。重要的是，ASCVD是NASH患者独立于传统危险因素之外的主要死因。然而，NAFLD/NASH与ASCVD之间的病理生理学联系仍知之甚少。虽然血脂异常是这两种疾病共有的常见危险因素，但降低循环LDL胆固醇的治疗方法对NASH大多无效。虽然目前尚无获批用于治疗NASH的药物疗法，但一些最先进的候选药物会加剧致动脉粥样硬化性血脂异常，引发人们对其心血管不良后果的担忧。在这篇综述中，我们阐述了目前在理解NAFLD/NASH与ASCVD之间联系机制方面的差距，探索同时模拟这两种疾病的策略，评估可能有助于诊断这两种疾病的新兴生物标志物，并讨论可能针对这两种疾病的研究方法和正在进行的临床试验。
