ACE2 inhibits proliferation of smooth muscle cell through AT1R and its downstream signaling pathway

To investigate the effect of the angiotensin converting enzyme 2 (ACE2) on AT1R expression, ERK1/2 and STAT3 protein phosphorylation in rat vascular smooth muscle cells (VSMCs) was studied. VSMCs were transfected with a lentiviral vector including the ACE2 gene and with siRNA to regulate the level of ACE2 in VSMCs. The levels of mRNA and proteins of ACE2, AT1R, ERK1/2, p-ERK1/2, STAT3, and p-STAT3 in VSMCs were examined using real-time PCR and western blot. The proliferation of VSMCs was observed by CCK-8 assay and BrdU measurement. Upregulation of ACE2 inhibited the growth of cells elicited by angiotensin II (Ang II). ACE2 significantly suppressed the level of the AT1 receptor (AT1R) protein induced by Ang II and phosphorylated the ERK1/2 and STAT3 proteins in the downstream signaling pathway. The transcriptional and translational levels of ACE2 were significantly lower in the si-ACE2 group than in the control group. The level of AT1R mRNA and protein, both with the phosphorylation expression of ERK1/2 and STAT3 protein in the siACE2 group and the Ang II group, were significantly enhanced than those in the control group. ACE2 significantly inhibited the growth of VSMCs. ACE2 inhibited the proliferation of VSMCs by suppressing AT1R and the downstream ERK1/2 and STAT3 signaling axes. Also, Ang II enhanced the level of AT1R and phosphorylated ERK1/2 and STAT3 by inhibiting the level of the ACE2 mRNA and protein.