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

doi:10.1016/j.isci.2024.109510

The activation of LBH-CRYAB signaling promotes cardiac protection against I/R injury by inhibiting apoptosis and ferroptosis

iScience. 2024 Mar 15;27(5):109510. doi: 10.1016/j.isci.2024.109510. eCollection 2024 May 17.

Authors

Anbiao Wu^{1

2}, Chongbin Zhong¹, Xudong Song¹, Wen Yuan³, Mintian Tang³, Tao Shu¹, Houda Huang¹, Pingzhen Yang¹, Qicai Liu¹

Affiliations

¹ 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.
² Beijing Institute of Basic Medical Sciences, Beijing 100850, People's Republic of China.
³ Experimental Animal Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, People's Republic of China.

Abstract

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.

Keywords: Biochemistry; Biological sciences; Cell biology; Natural sciences; Physiology.