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Small heat shock proteins in redox metabolism: implications for cardiovascular diseases. Int J Biochem Cell Biol 2012 Oct;44(10):1632-45

Date

06/20/2012

Pubmed ID

22710345

Pubmed Central ID

PMC3412898

DOI

10.1016/j.biocel.2012.06.006

Scopus ID

2-s2.0-84864437102   47 Citations

Abstract

A timely review series on small heat shock proteins has to appropriately examine their fundamental properties and implications in the cardiovascular system since several members of this chaperone family exhibit robust expression in the myocardium and blood vessels. Due to energetic and metabolic demands, the cardiovascular system maintains a high mitochondrial activity but irreversible oxidative damage might ensue from increased production of reactive oxygen species. How equilibrium between their production and scavenging is achieved becomes paramount for physiological maintenance. For example, heat shock protein B1 (HSPB1) is implicated in maintaining this equilibrium or redox homeostasis by upholding the level of glutathione, a major redox mediator. Studies of gain or loss of function achieved by genetic manipulations have been highly informative for understanding the roles of those proteins. For example, genetic deficiency of several small heat shock proteins such as HSPB5 and HSPB2 is well-tolerated in heart cells whereas a single missense mutation causes human pathology. Such evidence highlights both the profound genetic redundancy observed among the multigene family of small heat shock proteins while underscoring the role proteotoxicity plays in driving disease pathogenesis. We will discuss the available data on small heat shock proteins in the cardiovascular system, redox metabolism and human diseases. From the medical perspective, we envision that such emerging knowledge of the multiple roles small heat shock proteins exert in the cardiovascular system will undoubtedly open new avenues for their identification and possible therapeutic targeting in humans. This article is part of a Directed Issue entitled: Small HSPs in physiology and pathology.

Author List

Christians ES, Ishiwata T, Benjamin IJ

Author

Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cardiovascular Diseases
Cardiovascular System
Gene Expression Regulation, Developmental
Heat-Shock Proteins, Small
Humans
Mutation
Oxidation-Reduction
Oxidative Stress
Proteostasis Deficiencies
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