NCOR1 deficiency in mouse smooth muscle attenuates hypertension and vascular remodeling.

Smooth muscle nuclear receptor corepressor 1 (NCOR1) is implicated in phenotype modulation and aortic aneurysms, but its role in blood pressure regulation remains unclear. In the present study, using smooth muscle NCOR1 knockout male mice in combination with an angiotensin II-induced hypertensive mouse model, we found that NCOR1 deficiency reduced blood pressure and attenuated vascular remodeling. NCOR1 deficiency also alleviated age-related hypertension in aged male mice. Using inducible NCOR1-knockout male mice, we found that the deletion of smooth muscle NCOR1 prevents further exacerbation of hypertension. Compared with control VSMCs, NCOR1 deficient-vascular smooth muscle cells (VSMCs) exhibited less proliferation, migration, and contraction. Mechanistically, NCOR1 deficiency downregulated the expression of adhesion-related genes and impaired integrin signaling pathway in VSMCs. Collectively, our results indicate that NCOR1 regulates the expression of integrins in VSMCs, controls the proliferation, migration, and contraction of VSMCs, and finally affects blood pressure and vascular remodeling in male mice.