Tanshinone IIA suppresses endoplasmic reticulum stress-induced apoptosis of high glucose-conditioned vascular endothelial cells by regulating microRNA-133/RAC-1 pathway

Main Article Content

Lele Yang
Xiaofen Wu
Xiaoling Song
Decheng Pan

Keywords

tanshinone IIA, microRNA-133, RAC-1, endoplasmic reticulum stress, apoptosis, human umbilical vein endothelial cells

Abstract

Cellular stress caused by abnormal accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) is becoming a possible driver of cardiovascular diseases. The primary aim of our study was to explore Tanshinone IIA (Tan IIA)-induced protection against ER-induced apoptosis of human umbilical vein endothelial cells (HUVECs). HUVECs were treated with high glucose (HG), administrated with Tan IIA (2.5, 5, and 10 μM), and transfected with microRNA-133 (miR-133) mimic or inhibitor. Then cell viability was evaluated by MTT assay, the release of lactate dehydrogenase (LDH) was measured by detection kit, and ER stress was analyzed by Western blot measurement of ER stress-related indicators. Cell apoptosis was observed through flow cytometry and Western blot analysis of apoptosis-related markers. miR-133 and RAC-1 expressions in HUVECs were assessed. For HUVECs, HG inhibited cellular survival, promoted the release of LDH, apoptosis and ER stress, down-regulated miR-133, and up-regulated RAC-1. We demonstrated that Tan IIA reverted the damage of HG to HUVECs in a concentration-dependent manner. miR-133 could negatively regulate RAC-1 expression, and Tan IIA inhibited RAC-1 expression by elevating miR-133, thereby reducing the damage of HG to HUVECs. Tan IIA regulates miR-133–RAC-1 axis to reduce the apoptosis caused by ER stress in HG-induced HUVECs, which could provide new insights for treating cardiovascular diseases.

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