From the Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN (K.C.V.); and Marc and Ruti Bell Vascular Biology and Disease Program, Department of Medicine, New York University School of Medicine, New York, NY (K.J.M.).
Circ Res. 2013 Nov 8;113(11):1189-91. doi: 10.1161/CIRCRESAHA.113.302732.
The plasma level of apolipoprotein B (apoB) is among the strongest risk factors for coronary artery disease. Microsomal triglyceride transfer protein (MTP) plays a key role in the lipidation of nascent apoB and the secretion of apoB-containing lipoproteins enriched with triglycerides and is thus a promising target for the treatment of hyperlipidemia. Yet, the development of MTP inhibitors to lower plasma lipid concentrations has been hindered by adverse effects on hepatic steatosis. A study recently published in Nature Medicine identifies microRNA-30c (miR-30c) as a potent repressor of MTP that controls plasma apoB-containing lipoprotein levels, in addition to decreasing hepatic lipid synthesis through direct targeting of lysophosphatidylglycerol acyltransferase 1 (LPGAT1). These findings identify miR-30c as a novel therapeutic target that coordinately reduces lipid biosynthesis and lipoprotein secretion to suppress circulating apoB lipoproteins, while sparing the liver from steatosis.
载脂蛋白 B（apoB）的血浆水平是冠状动脉疾病的最强危险因素之一。微粒体甘油三酯转移蛋白（MTP）在新生 apoB 的脂质化和富含甘油三酯的 apoB 载脂蛋白的分泌中起关键作用，因此是治疗高脂血症的有前途的靶点。然而，由于对肝脂肪变性的不良影响，MTP 抑制剂降低血浆脂质浓度的发展受到阻碍。最近在《自然医学》杂志上发表的一项研究确定 microRNA-30c（miR-30c）是一种有效的 MTP 抑制剂，它可以控制载脂蛋白 B 的血浆脂蛋白水平，此外，通过直接靶向溶血磷脂酰甘油酰基转移酶 1（LPGAT1），还可以减少肝内脂质合成。这些发现确定 miR-30c 是一种新的治疗靶点，它可以协调降低脂质生物合成和脂蛋白分泌，以抑制循环 apoB 脂蛋白，同时使肝脏免受脂肪变性。
