Shear-Sensitive lncRNA AF131217.1 Inhibits Inflammation in HUVECs via Regulation of KLF4

Abstract

Atherosclerosis is one of the most common vascular diseases, and inflammation participates in all stages of its progression. Laminar shear stress protects arteries from atherosclerosis and reduces endothelial inflammation. Long noncoding RNAs have emerged as critical regulators in many diseases, including atherosclerosis. However, the expression and functions of long noncoding RNAs subjected to laminar shear stress in endothelial cells remain unclear. This study aimed to reveal the mechanism by which shear stress–regulated long noncoding RNAs contribute to anti-inflammation. In this study, we identified a novel long noncoding RNA AF131217.1, which was upregulated after laminar shear stress treatment in human umbilical vein endothelial cells. Knockdown of AF131217.1 inhibited flow-mediated reduction of monocyte adhesion VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) expression and inhibited flow-mediated enhancement of flow-responsive expression of KLF (Kruppel-like factor) 2 and eNOS (endothelial NO synthase). Furthermore, TNF-&agr; (tumor necrosis factor-&agr;) was used to induce an inflammatory response in human umbilical vein endothelial cells. Knockdown of AF131217.1 promoted ICAM-1 and VCAM-1 expression, as well as changes in monocyte adhesion and KLF2 and eNOS expression induced by TNF-&agr;. Mechanistic investigations indicated that AF131217.1 acted as a competing endogenous RNA for miR-128-3p, leading to regulation of its target gene KLF4. In conclusion, our study demonstrates for the first time that laminar shear stress regulates the expression of AF131217.1 in human umbilical vein endothelial cells, and the AF131217.1/miR-128-3p/KLF4 axis plays a vital role in atherosclerosis development.