Angptl2 gene knockdown is critical for abolishing angiotensin II-induced vascular smooth muscle cell proliferation and migration

Abstract

Angiopoietin-like 2 (Angptl2) is reported to be correlated with cardiovascular diseases, but its role in hypertension remains unclear. This study aimed to investigate the role and potential mechanism of Angptl2 in hypertension. Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were used to detect the expression of Angptl2. Angiotensin II (Ang II) stimulates vascular smooth muscle cells (VSMCs) to mimic hypertension in vitro. Cell proliferation, migration, and invasion abilities were determined using CCK-8, cell colony formation, wound healing, and transwell assays, respectively. The cell cycle distribution was detected by flow cytometry. The expression of Ki67 was determined by immunofluorescence, and protein expression was measured using western blotting. Angptl2 was found to be elevated in hypertensive rats in vivo and in VSMCs upon Ang II stimulation in vitro. Angptl2 knockdown suppressed cell proliferation, colony formation, cell migration, and invasion as well as the downregulation of Ki67. Additionally, Angptl2 knockdown hindered cell cycle progression and downregulated protein expression of CDK2/4 and cyclin D1, but upregulated p21 expression. Furthermore, Angptl2 knockdown inhibited activation of the NLRP3 inflammasome. Our findings suggest that Angptl2 knockdown suppresses VSMC proliferation, migration, and invasion induced by Ang II. Angptl2 may be a new target for vascular remodeling in hypertension.