Center for Translational Medicine, Jefferson Medical College, Philadelphia, PA, USA.
Center for Translational Medicine, Jefferson Medical College, Philadelphia, PA, USA; Laboratory for Molecular and Translational Cardiology, Department of Internal Medicine III, University of Heidelberg, INF 350, 69120 Heidelberg, Germany; DZHK (German Center for Cardiovascular Research), Partner site Heidelberg/Mannheim, Heidelberg University Hospital, INF 410, 69120 Heidelberg, Germany.
FEBS Lett. 2014 Mar 18;588(6):906-14. doi: 10.1016/j.febslet.2014.01.033. Epub 2014 Jan 31.
Exposure to pro-inflammatory cytokines, such as Angiotensin II, endothelin-1 or TNF leads to endothelial dysfunction, characterized by the reduced production of nitric oxide via endothelial nitric oxide synthase (eNOS). We recently identified the Ca(2+) binding protein S100A1 as an essential factor required for eNOS activity. Here we report that pro-inflammatory cytokines down-regulate expression of S100A1 in primary human microvascular endothelial cells (HMVECs) via induction of microRNA-138 (miR-138), in a manner that depends on the stabilization of HIF1-α. We show that loss of S100A1 in ECs reduces stimulus-induced NO production, which can be prevented by inhibition of miR-138. Our study suggests that targeting miR-138 might be beneficial for the treatment of cardiovascular disease.
炎症细胞因子（如血管紧张素 II、内皮素-1 或 TNF）的暴露可导致内皮功能障碍，其特征是内皮型一氧化氮合酶 (eNOS) 产生的一氧化氮减少。我们最近发现钙结合蛋白 S100A1 是 eNOS 活性所必需的重要因素。在这里，我们报告说，炎症细胞因子通过诱导 microRNA-138（miR-138）下调原代人微血管内皮细胞（HMVEC）中 S100A1 的表达，这种方式依赖于 HIF1-α 的稳定。我们表明，EC 中 S100A1 的缺失会减少刺激诱导的 NO 产生，而 miR-138 的抑制可防止这种情况发生。我们的研究表明，针对 miR-138 可能有益于心血管疾病的治疗。
