Abstract
Cardiovascular diseases (CVDs) are the leading cause of death globally, representing approximately 32% of all deaths worldwide. Molecular chaperones are involved in heart protection against stresses and age-mediated accumulation of toxic misfolded proteins by regulation of the protein synthesis/degradation balance and refolding of misfolded proteins, thus supporting the high metabolic demand of the heart cells. Heat shock protein 90 (HSP90) is one of the main cardioprotective chaperones, represented by cytosolic HSP90a and HSP90b, mitochondrial TRAP1 and ER-localised Grp94 isoforms. Currently, the main way to study the functional role of HSPs is the application of HSP inhibitors, which could have a different way of action. In this review, we discussed the recently investigated role of HSP90 proteins in cardioprotection, atherosclerosis, CVDs development and the involvements of HSP90 clients in the activation of different molecular pathways and signalling mechanisms, related to heart ageing.
Highlights
Cardiovascular diseases (CVDs) are the leading cause of death worldwide
We focus on the recently investigated role of Heat shock protein 90 (HSP90) proteins in CVDs development, mechanisms of HSP90s-mediated cardioprotection and discuss molecular pathways and signalling mechanisms related to heart ageing
Application of HSP90 inhibitor CTPR390 prevents binding of HSP90 to its client TGFβ, which resulted in reduced motility of myocardial TGFβ-activated fibroblasts, blocked collagen expression and improved angiotensin-II (AngII) -induced cardiac myocardial fibrosis in vivo in a pro-fibrotic mouse model [43]
Summary
Cardiovascular diseases (CVDs) are the leading cause of death worldwide. CVDs are defined as a group of heart and blood vessels disorders, including coronary heart disease, peripheral arterial disease, pulmonary embolism, deep vein thrombosis, cerebrovascular diseases and others. Ageing is a normal physiological process, which is characterised by a general decline in the efficacy of protein quality control systems and disruptions of protein and mitochondria degradation pathways, resulting in a wide range of age-associated cardiac dysfunction and a high risk of CVDs development [7]. Molecular chaperones are one of the crucial classes of proteins, involved in heart protection against stresses- and age-mediated accumulation of toxic misfolded proteins by regulation of the protein synthesis/degradation balance and refolding of misfolded proteins [8]. We focus on the recently investigated role of HSP90 proteins in CVDs development, mechanisms of HSP90s-mediated cardioprotection and discuss molecular pathways and signalling mechanisms related to heart ageing
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