OBJECTIVETo investigate the process and mechanism of neointimal formation, the level of angiotensin II and angiotensin (1-7), the expression of angiotensin converting enzyme 2(ACE2), angiotensin II type 1 receptor (AT(1)R), extracellular signal regulated kinase (ERK) and the effects of valsartan on them after aortic balloon injury in rats.

METHODSAortic endothelial denudation of rats was induced by 2F balloon catheter. Thirty-six rats were randomly allocated into three groups: Group 1 (n = 12): controls; Group 2 (n = 12): aortic balloon injury; Group 3 (n = 12): valsartan (20 mg×kg(-1)×d(-1)) given from 1 day before injury to 14 and 28 days after aortic injury. The expression of ACE2 and AT1, the level of P-ERK, AngII, Ang(1-7) and intimal thickening were investigated by RT-PCR technique, immunohistochemistry, Western blot, radioimmunological method, enzyme linked immunosorbent assay (ELISA) and HE stain, respectively.

RESULTS(1) The proliferation of vascular smooth muscle cells (VSMC) and the intimal thickening were evidenced at day 14 and 28 after aortic balloon injury. (2) The mRNA and protein expressions of ACE2 decreased significantly, but AT(1)R mRNA and protein expression increased significantly at day 14 and 28 after balloon injury. (3) The level of AngII and p-ERK increased and Ang(1-7) reduced after balloon injury. (4) Valsartan not only attenuated the proliferation of VSMC and the intimal thickening but also upregulated the expression of ACE2 and the level of Ang(1-7) and downregulated the expression of AT(1)R and the level of AngII, p-ERK in this model.

CONCLUSIONIntimal thickening after balloon injury is linked with reduced expression of ACE2.Valsartan can inhibit the intimal thickening possibly by upregulating ACE2 and Ang(1-7) and downregulating AT(1) in this model.