Dihydrotanshinone I ameliorated angiotensin II-induced mitochondrial damage and oxidative stress in vascular smooth muscle cells

The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) initiated by Angiotensin II (AngII) is the key effects contributing to hypertension-related vascular lesions. Dihydrotanshinone I (DHTS), one of the active components of S. miltiorrhiza extract, has shown pharmacological activity for cardiovascular protection. However, the role of DHTS in AngII-stimulated damage to VSMCs has not been reported.

This study aimed to explore the potential effects and mechanisms of DHTS on VSMCs injury in hypertensive.

AngII significantly induced the cell proliferation, the accumulation of EDU-positive cells, an accelerated cell cycle, and migration in A7R5 cells, and these effects could be reversed by DHTS treatment. Furthermore, DHTS treatment reduced ROS generation and improved mitochondrial dysfunction in AngII-induced A7R5 cells. Mechanistically, DHTS post-transcriptionally suppressed Drp1 expression, and the reduced binding of HuR to Drp1 mRNA accounted for this result. Drp1 overexpression reversed the positive effects of DHTS on A7R5 cells under AngII stimulation.

Our findings suggested that DHTS could inhibit AngII-induced VSMC proliferation, migration, and oxidative stress while restoring mitochondrial function.