Valsartan attenuates intimal hyperplasia in balloon-injured rat aortic arteries through modulating the angiotensin-converting enzyme 2-angiotensin-(1–7)-Mas receptor axis

• The role of Mas receptor in valsartan against intimal hyperplasia is unclear.
• Protective role of valsartan correlates to activate ACE2-angiotensin-(1–7)-Mas axis.
• Valsartan also inhibits the ACE-angiotensin II-AT1 and p-ERK signaling pathways.

The role of the Mas receptor in the activity of valsartan against intimal hyperplasia is unclear. Herein, we investigated the role of the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1–7)-Mas receptor axis on the activity of valsartan against intimal hyperplasiain balloon-injured rat aortic arteries. Wistar rats were randomized equally into the sham control group, injured group, and injured plus valsartan (20 mg/kg/d)-treated group. Valsartan significantly attenuated the vascular smooth muscle cell proliferation and intimal and medial thickening on days 14 and 28 after injury. The angiotensin-(1–7) levels as well as ACE2 and Mas receptor mRNA/protein expression were significantly decreased in the injured rats, compared to the uninjured rats; meanwhile, the angiotensin II level as well as the ACE and AT1 receptor mRNA/protein expression were increased (all P < 0.05 or < 0.01). Additionally, the p-ERK protein expression was increased (P < 0.01). Treatment with valsartan significantly increased the angiotensin-(1–7) levels as well as ACE2 and Mas receptor mRNA/protein expression but decreased the angiotensin II level, ACE and AT1 receptor mRNA/protein expression, as well as the p-ERK protein expression, compared to the injured group (all P < 0.05 or < 0.01). These results suggest that valsartan attenuates neointimal hyperplasiain balloon-injured rat aortic arteries through activation of the ACE2-angiotensin-(1–7)-Mas axis as well as inhibition of the ACE-angiotensin II-AT1 and p-ERK pathways.

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