Fluid shear stress modulates endothelial inflammation by targeting LIMS2

Mechanosensitive genes regulate multiple cardiovascular pathophysiological processes and disorders; however, the role of flow-sensitive genes in atherosclerosis is still unknown. In this study, we identify LIM Zinc Finger Domain Containing 2 (LIMS2) that acts as a mechanosensitive gene downregulated by disturbed flow (d-flow) both in human endothelial cells (ECs) in vitro and in mice in vivo. Mechanistically, d-flow suppresses LIMS2 expression, which leads to endothelial inflammation by upregulating typical inflammatory factors, VCAM-1, and ICAM-1 in human ECs. The findings indicate that LIMS2, the new flow-sensitive gene, may help us to find a new insight to explain how d-flow caused endothelial inflammation and provide a new therapeutic approach for atherosclerosis in the future. Impact statement: Whereas we all know that atherosclerosis is the most main common reason of death all over the world, the mechanism of atherosclerosis is still unclear. Recently, more and more evidence indicate that atherosclerosis is a kind of flow-dependent disease, and plenty of mechanosensitive genes have been mentioned in it. Here, we identified for the first time that LIMS2 is a novel flow-sensitive gene and inhibits inflammation by modulating inflammatory factors, VCAM-1, and ICAM-1 in endothelial cells. It will help us to understand the connection between endothelial shear stress and endothelial inflammation deeply; certainly, LIMS2 may also act as a potential target for flow-dependent atherosclerosis.