Small RNA overcomes the challenges of therapeutic targeting of microsomal triglyceride transfer protein.
Small RNA overcomes the challenges of therapeutic targeting of microsomal triglyceride transfer protein.
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DOI：
10.1161/circresaha.113.302732
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发表时间：
2013-11-08
影响因子：
20.1
通讯作者：
Moore KJ
中科院分区：
文献类型：
--
作者：
Vickers KC;Moore KJ
血浆载脂蛋白B（apoB）水平是冠心病最强的危险因素之一。微粒体甘油三酯转移蛋白（MTP）在新生apoB的脂化和富含甘油三酯的含apoB的脂蛋白的分泌中起关键作用，因此是治疗高脂血症的有希望的靶点。然而，MTP抑制剂降低血浆脂质浓度的发展受到肝脂肪变性不良反应的阻碍。最近发表在Nature Medicine上的一项研究将microRNA-30 c（miR-30 c）鉴定为MTP的有效阻遏物，除了通过直接靶向溶血磷脂酰甘油酰基转移酶1（LPGAT 1）减少肝脏脂质合成外，还控制血浆含apoB的脂蛋白水平。这些发现将miR-30 c确定为一种新的治疗靶点，其协调减少脂质生物合成和脂蛋白分泌以抑制循环apoB脂蛋白，同时使肝脏免于脂肪变性。
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.