Hsp22 Deficiency Induces Age-Dependent Cardiac Dilation and Dysfunction by Impairing Autophagy, Metabolism, and Oxidative Response

Autor: Wenqian Wu, Xiaonan Sun, Xiaomeng Shi, Lo Lai, Charles Wang, Mingxin Xie, Gangjian Qin, Hongyu Qiu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Antioxidants, Vol 10, Iss 10, p 1550 (2021)
Druh dokumentu: article
ISSN: 2076-3921
DOI: 10.3390/antiox10101550
Popis: Heat shock protein 22 (Hsp22) is a small heat shock protein predominantly expressed in skeletal and cardiac muscle. Previous studies indicate that Hsp22 plays a vital role in protecting the heart against cardiac stress. However, the essential role of Hsp22 in the heart under physiological conditions remains largely unknown. In this study, we used an Hsp22 knockout (KO) mouse model to determine whether loss of Hsp22 impairs cardiac growth and function with increasing age under physiological conditions. Cardiac structural and functional alterations at baseline were measured using echocardiography and invasive catheterization in Hsp22 KO mice during aging transition compared to their age-matched wild-type (WT) littermates. Our results showed that Hsp22 deletion induced progressive cardiac dilation along with declined function during the aging transition. Mechanistically, the loss of Hsp22 impaired BCL-2–associated athanogene 3 (BAG3) expression and its associated cardiac autophagy, undermined cardiac energy metabolism homeostasis and increased oxidative damage. This study showed that Hsp22 played an essential role in the non-stressed heart during the early stage of aging, which may bring new insight into understanding the pathogenesis of age-related dilated cardiomyopathy.
Databáze: Directory of Open Access Journals