J Clin Invest. 2019 Oct 1;129(10):4074-4076. doi: 10.1172/JCI131333.
In this issue of the JCI, Kanter et al. make a strong case for implicating apolipoprotein C3 (APOC3) as a central player in atherosclerotic cardiovascular disease that is commonly seen in individuals with type 1 diabetes mellitus (T1DM). Kanter and colleagues suggest that insulin deficiency elevates plasma APOC3 as well as atherogenic triglyceride-rich (TG-rich) lipoproteins (TRLs). Using two mouse models of T1DM, the authors investigated APOC3-mediated inhibition of both TG hydrolysis by lipoprotein lipase and hepatic uptake of remnant lipoproteins. They suggest that poorly catabolized lipoproteins, enriched in both APOC3 and APOE content, are particularly atherogenic. Notably, treating both mouse models with an APOC3 antisense oligonucleotide lowered both plasma APOC3 and TRLs, and prevented atherosclerosis. These impactful mouse studies were supported by the initial finding that APOC3 predicted coronary artery disease events in participants of the prospective Coronary Artery Calcification in Type 1 Diabetes study with normal TG levels.
在本期 JCI 中，Kanter 等人提出了一个强有力的观点，即载脂蛋白 C3（APOC3）是 1 型糖尿病（T1DM）患者常见的动脉粥样硬化性心血管疾病的关键因素。Kanter 及其同事认为，胰岛素缺乏会导致血浆 APOC3 以及致动脉粥样硬化性富含甘油三酯（TG）的脂蛋白（TRLs）升高。作者使用两种 T1DM 小鼠模型，研究了 APOC3 对脂蛋白脂肪酶水解 TG 以及肝脏摄取残粒脂蛋白的抑制作用。他们认为，代谢不良的脂蛋白富含 APOC3 和 APOE，尤其具有致动脉粥样硬化性。值得注意的是，用 APOC3 反义寡核苷酸治疗两种小鼠模型均降低了血浆 APOC3 和 TRL，从而预防了动脉粥样硬化。这项有影响力的小鼠研究得到了初步发现的支持，即载脂蛋白 C3 可预测前瞻性 1 型糖尿病冠状动脉钙化研究中 TG 水平正常的参与者的冠状动脉疾病事件。
