Emerging role of VCP/p97 in cardiovascular diseases: novel insights and therapeutic opportunities

Author:

Shu Hongyang1ORCID,Peng Yizhong2,Hang Weijian1,Zhou Ning1,Wang Dao Wen1

Affiliation:

1. Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China

2. Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China

Abstract

Valosin-containing protein (VCP/p97) is a member of the conserved type II AAA+ (ATPases associated with diverse cellular activities) family of proteins with multiple biological functions, especially in protein homeostasis. Mutations in VCP/p97 are reportedly related to unique autosomal dominant diseases, which may worsen cardiac function. Although the structure of VCP/p97 has been clearly characterized, with reports of high abundance in the heart, research focusing on the molecular mechanisms underpinning the roles of VCP/p97 in the cardiovascular system has been recently undertaken over the past decades. Recent studies have shown that VCP/p97 deficiency affects myocardial fibers and induces heart failure, while overexpression of VCP/p97 eliminates ischemia/reperfusion injury and relieves pathological cardiac hypertrophy caused by cardiac pressure overload, which is related to changes in the mitochondria and calcium overload. However, certain studies have drawn opposing conclusions, including the mitigation of ischemia/reperfusion injury via inhibition of VCP/p97 ATPase activity. Nevertheless, these emerging studies shed light on the role of VCP/p97 and its therapeutic potential in cardiovascular diseases. In other words, VCP/p97 may be involved in the development of cardiovascular disease, and is anticipated to be a new therapeutic target. This review summarizes current findings regarding VCP/p97 in the cardiovascular system for the first time, and discusses the role of VCP/p97 in cardiovascular disease.

Publisher

Portland Press Ltd.

Subject

Biochemistry

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