Temel Ryan E, Brown J Mark
Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40536-0509, USA.
Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
Trends Pharmacol Sci. 2015 Jul;36(7):440-51. doi: 10.1016/j.tips.2015.04.002. Epub 2015 Apr 27.
Cardiovascular disease (CVD) remains the largest cause of mortality in most developed countries. Although recent failed clinical trials and Mendelian randomization studies have called into question the high-density lipoprotein (HDL) hypothesis, it remains well accepted that stimulating the process of reverse cholesterol transport (RCT) can prevent or even regress atherosclerosis. The prevailing model for RCT is that cholesterol from the artery wall must be delivered to the liver where it is secreted into bile before leaving the body through fecal excretion. However, many studies have demonstrated that RCT can proceed through a non-biliary pathway known as transintestinal cholesterol excretion (TICE). The goal of this review is to discuss the current state of knowledge of the TICE pathway, with emphasis on points of therapeutic intervention.
心血管疾病(CVD)仍然是大多数发达国家最大的死因。尽管最近临床试验和孟德尔随机化研究的失败对高密度脂蛋白(HDL)假说提出了质疑,但人们仍然普遍认为,刺激逆向胆固醇转运(RCT)过程可以预防甚至逆转动脉粥样硬化。RCT的主流模型是,动脉壁中的胆固醇必须被输送到肝脏,在那里它被分泌到胆汁中,然后通过粪便排泄离开身体。然而,许多研究表明,RCT可以通过一种称为肠道胆固醇排泄(TICE)的非胆汁途径进行。这篇综述的目的是讨论TICE途径的当前知识状态,重点是治疗干预点。