The dual role of heat shock protein 60 in Cardiac diseases: From mitochondrial chaperone to extracellular immunomodulator — A review and future perspectives

The abundance of mitochondria in cardiac cells is vital, as they are extremely important for adenosine triphosphate (ATP) synthesis, maintaining redox balance, regulating calcium homeostasis, and facilitating lipid synthesis. One of the most abundant proteins in the mitochondria is the heat shock protein 60 (Hsp60), a chaperone that plays a crucial role in the translocation and folding of mitochondrial proteins. As a stress protein, Hsp60 increases when the heart muscle is under pressure, such as during a heart attack or heart failure. Recently, our research group has demonstrated that Hsp60 can be released under stress conditions in small and large vesicles or freely in the cell culture medium. In this review, we have analysed the published literature to determine whether Hsp60 may function as a damage-associated molecular pattern (DAMP) protein capable of interacting with Toll-like receptors (TLRs) to modulate immune responses, and we hypothesised that Hsp60 released in small extracellular vesicles may act as an immunomodulator.