Carcamo-Orive Ivan, Huang Ngan F, Quertermous Thomas, Knowles Joshua W
From the Department of Medicine and Cardiovascular Institute (I.C.-O., T.Q., J.W.K.) and Department of Cardiothoracic Surgery and Cardiovascular Institute (N.F.H.), Stanford University School of Medicine, CA; and Veterans Affairs Palo Alto Health Care System, CA (N.F.H.).
Arterioscler Thromb Vasc Biol. 2017 Nov;37(11):2038-2042. doi: 10.1161/ATVBAHA.117.309291. Epub 2017 Jul 20.
Insulin resistance leads to a number of metabolic and cellular abnormalities including endothelial dysfunction that increase the risk of vascular disease. Although it has been particularly challenging to study the genetic determinants that predispose to abnormal function of the endothelium in insulin-resistant states, the possibility of deriving endothelial cells from induced pluripotent stem cells generated from individuals with detailed clinical phenotyping, including accurate measurements of insulin resistance accompanied by multilevel omic data (eg, genetic and genomic characterization), has opened new avenues to study this relationship. Unfortunately, several technical barriers have hampered these efforts. In the present review, we summarize the current status of induced pluripotent stem cell-derived endothelial cells for modeling endothelial dysfunction associated with insulin resistance and discuss the challenges to overcoming these limitations.
胰岛素抵抗会导致多种代谢和细胞异常,包括内皮功能障碍,从而增加血管疾病的风险。尽管研究导致胰岛素抵抗状态下内皮功能异常的遗传决定因素极具挑战性,但从具有详细临床表型的个体(包括准确测量胰岛素抵抗并伴有多组学数据,如基因和基因组特征)产生的诱导多能干细胞中获取内皮细胞的可能性,为研究这种关系开辟了新途径。不幸的是,一些技术障碍阻碍了这些努力。在本综述中,我们总结了用于模拟与胰岛素抵抗相关的内皮功能障碍的诱导多能干细胞衍生内皮细胞的现状,并讨论克服这些限制所面临的挑战。