The activation of LBH-CRYAB signaling promotes cardiac protection against I/R injury by inhibiting apoptosis and ferroptosis
Anbiao Wu,
Chongbin Zhong,
Xudong Song,
Wen Yuan,
Mintian Tang,
Tao Shu,
Houda Huang,
Pingzhen Yang,
Qicai Liu
Affiliations
Anbiao Wu
Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Laboratory of Heart Center, Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, People’s Republic of China; Beijing Institute of Basic Medical Sciences, Beijing 100850, People’s Republic of China
Chongbin Zhong
Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Laboratory of Heart Center, Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, People’s Republic of China
Xudong Song
Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Laboratory of Heart Center, Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, People’s Republic of China
Wen Yuan
Experimental Animal Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, People’s Republic of China
Mintian Tang
Experimental Animal Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, People’s Republic of China
Tao Shu
Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Laboratory of Heart Center, Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, People’s Republic of China
Houda Huang
Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Laboratory of Heart Center, Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, People’s Republic of China
Pingzhen Yang
Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Laboratory of Heart Center, Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, People’s Republic of China; Corresponding author
Qicai Liu
Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Laboratory of Heart Center, Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, People’s Republic of China; Corresponding author
Summary: Myocardial ischemia-reperfusion (I/R) injury stands out among cardiovascular diseases, and current treatments are considered unsatisfactory. For cardiomyocytes (CMs) in ischemic tissues, the upregulation of Limb-bud and Heart (LBH) and αB-crystallin (CRYAB) and their subsequent downregulation in the context of cardiac fibrosis have been verified in our previous research. Here, we focused on the effects and mechanisms of activated LBH-CRYAB signaling on damaged CMs during I/R injury, and confirmed the occurrence of mitochondrial apoptosis and ferroptosis during I/R injury. The application of inhibitors, ectopic expression vectors, and knockout mouse models uniformly verified the role of LBH in alleviating both apoptosis and ferroptosis of CMs. p53 was identified as a mutual downstream effector for both LBH-CRYAB-modulated apoptosis and ferroptosis inhibition. In mouse models, LBH overexpression was confirmed to exert enhanced cardiac protection against I/R-induced apoptosis and ferroptosis, suggesting that LBH could serve as a promising target for the development of I/R therapy.
