Macrophage NCOR1 Deficiency Ameliorates Myocardial Infarction and Neointimal Hyperplasia in Mice.

Journal of the American Heart Association 2020 Aug 04

filter terms:

Background NCOR1 (nuclear receptor corepressor 1) is an essential coregulator of gene transcription. It has been shown that NCOR1 in macrophages plays important roles in metabolic regulation. However, the function of macrophage NCOR1 in response to myocardial infarction (MI) or vascular wire injury has not been elucidated. Methods and Results Here, using macrophage Ncor1 knockout mouse in combination with a mouse model of MI, we demonstrated that macrophage NCOR1 deficiency significantly reduced infarct size and improved cardiac function after MI. In addition, macrophage NCOR1 deficiency markedly inhibited neointimal hyperplasia and vascular remodeling in a mouse model of arterial wire injury. Inflammation and macrophage proliferation were substantially attenuated in hearts and arteries of macrophage Ncor1 knockout mice after MI and arterial wire injury, respectively. Cultured primary macrophages from macrophage Ncor1 knockout mice manifested lower expression of inflammatory genes upon stimulation by interleukin-1β, interleukin-6, or lipopolysaccharide, together with much less activation of inflammatory signaling cascades including signal transducer and activator of transcription 1 and nuclear factor-κB. Furthermore, macrophage Ncor1 knockout macrophages were much less proliferative in culture, with inhibited cell cycle progression compared with control cells. Conclusions Collectively, our data have demonstrated that NCOR1 is a critical regulator of macrophage inflammation and proliferation and that deficiency of NCOR1 in macrophages attenuates MI and neointimal hyperplasia. Therefore, macrophage NCOR1 may serve as a potential therapeutic target for MI and restenosis.

Citation

Lin-Juan Du, Jian-Yong Sun, Wu-Chang Zhang, Yong-Li Wang, Hong Zhu, Ting Liu, Ming-Zhu Gao, Chen Zheng, Yu-Yao Zhang, Yuan Liu, Yan Liu, Shuai Shao, Xue-Qing Zhang, Qibin Leng, Johan Auwerx, Sheng-Zhong Duan. Macrophage NCOR1 Deficiency Ameliorates Myocardial Infarction and Neointimal Hyperplasia in Mice. Journal of the American Heart Association. 2020 Aug 04;9(15):e015862