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

Wenqian Wu,Charles Wang,Xiaonan Sun,Hongyu Qiu,Lo Lai,Gangjian Qin,Xiaomeng Shi,Mingxin Xie

doi:10.3390/antiox10101550

Abstract

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.

Highlights

Heat shock proteins (Hsps) comprise a large family of ubiquitously expressed stress proteins that constitute an endogenous stress response system to protect cells against insults such as hypoxia and ischemia
The results showed that cardiac myocyte size, represented by cross-sectional area (CSA), was significantly increased in the older Heat shock protein 22 (Hsp22) KO mice compared to their age-matched WT mice (Figure 1K)
The results showed that cardiac myocyte size, represented by CSA, was significantly increased in the older Hsp22 KO mice compared to their age-matched WT mice (Figure 1K). 6 of 20

Summary

Introduction

Heat shock proteins (Hsps) comprise a large family of ubiquitously expressed stress proteins that constitute an endogenous stress response system to protect cells against insults such as hypoxia and ischemia. Heat shock protein 22 (Hsp22), known as protein kinase. A dramatic upregulation of cardiac Hsp expression has been observed in well-characterized animal models of cardiovascular disease and patients diagnosed with various forms of cardiac disorders, including acute and chronic myocardial ischemic injuries and pressure overload-induced cardiac hypertrophy [6,7]. Our previous studies demonstrated that Hsp overexpression could protect the heart against ischemic injury [8]. Hsp deletion accelerates cardiac dysfunction and ventricular remodeling leading to heart failure (HF) in a pressure overload-induced

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Results

Conclusion