胰岛素对血管平滑肌α肌动蛋白基因变异的影响机制

Pathogenesis of Insulin Effects on Vascular Smooth Muscle Alpha-actin Gene Variation

胰岛素不仅能维持血管平滑肌细胞的静止形态,也能促进血管平滑肌细胞的迁移。胰岛素这种不同的效应是通过血管平滑肌细胞表型标志物α-平滑肌肌动蛋白实现的,因为α-平滑肌肌动蛋白在血管平滑肌细胞静止形态中高表达,而在血管平滑肌细胞迁移形态中低表达。胰岛素维持血管平滑肌细胞静止形态是通过磷脂酰肌醇激酶3途径实现的,而其促进血管平滑肌细胞迁移是通过活化蛋白激酶实现的。因此,在模拟胰岛素抵抗状态,即阻断磷脂酰肌醇激酶3信号通路并保留活化蛋白激酶信号通路,胰岛素可能失去维持血管平滑肌细胞的静止状态,取而代之的是促进血管平滑肌细胞的迁移。α-平滑肌肌动蛋白的变异能引发许多血管性疾病,包括冠心病、缺血性脑卒中等。α-平滑肌肌动蛋白的单基因也变异能引发弥漫性血管疾病,包含了动脉的阻塞及扩大,这在临床上对血管性疾病的研究和治疗有直接的指导作用。

Insulin maintains vascular smooth muscle cell （VSMC） quiescence and can also promote VSMC migration. The mechanisms by which insulin exerts these contrasting effects were examined using α-smooth muscle actin （α-SMA） as a marker of VSMC phenotype,because α-SMA is highly expressed in quiescent but not migratory VSMC. Insulin＇s ability to maintain VSMC quiescence is mediated via the PI3K pathway, whereas insulin promotes VSMC migration via the MAPK pathway. Thus, with impaired PI3K signaling and intact MAPK signaling, as seen in insulin resistance, insulin may lose its ability to maintain VSMC quiescence and instead promote VSMC migration. α-SMA mutations can have a diversity of vascular diseases, including coronary artery disease, ischemic strokes and so on. Diffuse vascular diseases resulting from either occluded or enlarged arteries can be caused by mutations in a single gene and have direct implications for clinical management and research on vascular diseases.