Heat Shock Protein 60 in Cardiovascular Physiology and Diseases

Abstract

Heat shock protein 60 (HSP60) is a highly conserved protein abundantly expressed in both prokaryotic and eukaryotic cells. In mammals, HSP60 has been primarily considered to reside in the mitochondria, where HSP60 and HSP10 form a complex and facilitate mitochondrial protein folding. However, HSP60 is also observed in the cytoplasm, the plasma membrane, and the extracellular space. HSP60 regulates a broad spectrum of cellular events including protein trafficking, peptide hormone signaling, cell survival, cell proliferation, inflammation, and immunization. In the cardiovascular system, growing evidence indicates that HSP60 could not only play an important role under physiological conditions, but also regulate the initiation and progression of heart failure and atherosclerosis. In this review, we focus on recent progress in understanding the function of HSP60 in cardiomyocytes, endothelial cells, and vascular smooth muscle cells (VSMCs), respectively, and discuss the related signaling pathways that have been found in these cells, so as to illustrate the role of HSP60 in the development of cardiovascular disease.

Proteomics of Extracellular Vesicles: Update on Their Composition, Biological Roles and Potential Use as Diagnostic Tools in Atherosclerotic Cardiovascular Diseases

“…Similarly, HSP70 is expressed in the cardiac exosomes and it is involved in the regulation of cardiomyocyte growth and survival under stress stimuli. Cardiac exosomes are also enriched for HSP60 which has an important role under physiological conditions, but it also plays a regulatory role in the progression of pathological conditions such as heart failure and atherosclerosis [ 153 ]. HSP60 in the exosomes is found to be attached to the exosome membrane, and after its release by cardiomyocytes via exosomes, extracellular HSP60 is generally considered as a damaging signal to the surrounding cardiac myocytes because it stimulates the release of TNF-α and IL-6 from cardiomyocytes and increases the expression of Toll-like receptor (TLR) 4 causing cardiac myocyte apoptosis [ 154 ].…”

Mitochondrial Chaperones and Proteases in Cardiomyocytes and Heart Failure

“…HSP60 is a highly conserved protein in both prokaryotic and eukaryotic cells and is abundantly expressed in cardiomyocytes alongside its co-chaperone HSP10 ( Duan et al, 2020 ). HSP60 is mainly localized in mitochondria, where it is widely recognized as a key player in regulating mitochondrial protein homeostasis ( Lin et al, 2007 ; Duan et al, 2020 ).…”

“…HSP60 is a highly conserved protein in both prokaryotic and eukaryotic cells and is abundantly expressed in cardiomyocytes alongside its co-chaperone HSP10 ( Duan et al, 2020 ). HSP60 is mainly localized in mitochondria, where it is widely recognized as a key player in regulating mitochondrial protein homeostasis ( Lin et al, 2007 ; Duan et al, 2020 ). HSP60 is also observed in the cytoplasm, plasma membrane, extracellular space, and in the bloodstream, where it may regulate cell apoptosis, proliferation, migration, and immune responses ( Lin et al, 2007 ; Henderson et al, 2013 ; Meng et al, 2018 ; Duan et al, 2019 , 2020 ).…”

“…HSP60 is mainly localized in mitochondria, where it is widely recognized as a key player in regulating mitochondrial protein homeostasis ( Lin et al, 2007 ; Duan et al, 2020 ). HSP60 is also observed in the cytoplasm, plasma membrane, extracellular space, and in the bloodstream, where it may regulate cell apoptosis, proliferation, migration, and immune responses ( Lin et al, 2007 ; Henderson et al, 2013 ; Meng et al, 2018 ; Duan et al, 2019 , 2020 ). To facilitate its folding and refolding capacity, the human HSP60 protein forms a symmetrical football complex with HSP10, and its bacteria homolog GroEL forms a barrel-like structure ( Ostermann et al, 1989 ; Horwich et al, 2006 ; Nisemblat et al, 2015 ).…”

Significance of exosomes in Cardiology: Heralds of cardioprotection

“…There is also an HSP60 mitochondrial form, which prevents the degradation of mitochondrial proteins through LONP1 (Lon peptidase 1). The decrease or deletion of mitochondrial HSP60 generates mitochondrial dysfunction and subsequent heart dilatation and failure 65 . HSP60 of exosomal origin binds to TLR4, which promotes the release of tumor necrosis factor alpha (TNF-a) and interleukin-6 (IL-6) 65 .…”