Smooth muscle NCOR1 deficiency attenuates hypertension and vascular remodeling
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Smooth muscle nuclear receptor corepressor 1 (NCOR1) plays an important role in phenotype modulation and aortic aneurysms. Nevertheless, its specific role in blood pressure regulation remains unknown. In the present study, we used smooth muscle NCOR1 knockout mice in combination with an angiotensin II-induced hypertensive mouse model and found that smooth muscle NCOR1 deficiency reduced systolic and diastolic blood pressure and attenuated vascular remodeling. Furthermore, smooth muscle NCOR1 deficiency alleviated age-related hypertension in aged mice. Using inducible NCOR1-knockout mice, we found that the deletion of smooth muscle NCOR1 exhibited a beneficial therapeutic effect on preexisting hypertension. Compared with control VSMCs, cultured NCOR1 deficient-vascular smooth muscle cells (VSMCs) exhibited less proliferation, migration, and contraction. Mechanistically, NCOR1 deficiency downregulated the expression of Itgb1 , Itgav , Tln , and Vcl and inhibited the activation of the integrin signaling pathway in VSMCs. In conclusion, our results indicate that NCOR1 regulated the expression of integrins in VSMCs, controlled the proliferation, migration, and contraction of VSMCs, and finally affected blood pressure and vascular remodeling in mice.