The Role of HSP90 Inhibitors in the Treatment of Cardiovascular Diseases

Abstract

Cardiovascular disease is the result of complicated pathophysiological processes in the tissues that make up the blood vessels and heart. Heat shock protein 90 (HSP90) can interact with 10% of the proteome and is the most widely studied molecular chaperone in recent years. HSP90 is extensively involved in the regulation of protein folding and intracellular protein stability, making HSP90 a hopeful target for the treatment of multiple cardiovascular diseases. Numerous client proteins of HSP90 have been identified in known cardiac disease pathways, including MAPK signaling, PI3K/AKT (PKB)/mTOR, and TNF-α signaling. Therefore, these pathways can be controlled by regulating HSP90. Among them, the activity of HSP90 can be regulated via numerous inhibitors. In this review, first, we will discuss the function of HSP90 and its role in pathological pathways. In addition, HSP90 plays a significant role in most cardiovascular diseases, including hypertension, pulmonary venous hypertension, atherosclerosis, and heart failure; next we will focus on this part. Finally, we will summarize the currently known HSP90 inhibitors and their potential in the treatment of heart disease.

The Potential Regenerative Effect of L-carnitine Pretreated Mesenchymal Stem Cells in Myocardial Infarction Through Modulating Apoptosis, Inflammation, and Cellular Differentiation

“…In addition, hsp90 was identified in various cardiac injury pathways such as PI3K/AKT (PKB)/mTOR, MAPK, and TNF-α signaling pathways. Therefore, hsp90 plays a significant role in various cardiovascular diseases including atherosclerosis and heart failure [82] as detected in the present study by overexpression in the DOX-treated group and a decrease in its level especially in the L-carnitine pre-treated-MSCs-group. TH regulates the rate of catecholamine synthesis.…”

Fibroblast-derived extracellular vesicles as trackable efficient transporters of an experimental nanodrug with fibrotic heart and lung targeting

“…Related to the protein content, we observed Hsp90 significantly augmented in mKate2 10K-EVs compared to mKate2 100K-EVs. Numerous client proteins of Hsp90 have been identified in known cardiac and lung disease pathways, including MAPK signaling, PI3K/AKT (PKB)/mTOR, and TNF-α signaling 60 .…”

A bioinformatics approach to elucidate conserved genes and pathways in C. elegans as an animal model for cardiovascular research

“…www.nature.com/scientificreports/ Its client proteins have been found to be involved in cardiac disease pathways such as MAPK signaling, TNF-α signaling, etc. 87 . A study of these proteins and signaling pathways using C. elegans ortholog can provide better insights into the molecular mechanism associated with the disease.…”