Emerging role of heat shock proteins in cardiovascular diseases.

Abstract

Heat Shock Proteins (HSPs) are evolutionarily conserved proteins from prokaryotes to eukaryotes. They are ubiquitous proteins involved in key physiological and cellular pathways (viz. inflammation, immunity and apoptosis). Indeed, the survivability of the cells under various stressful conditions depends on appropriate levels of HSP expression. There is a growing line of evidence for the role of HSPs in regulating cardiovascular diseases (CVDs) (viz. hypertension, atherosclerosis, atrial fibrillation, cardiomyopathy and heart failure). Furthermore, studies indicate that a higher concentration of circulatory HSP antibodies correlate to CVDs; some are even potential markers for CVDs. The multifaceted roles of HSPs in regulating cellular signaling necessitate unraveling their links to pathophysiology of CVDs. This review aims to consolidate our understanding of transcriptional (via multiple transcription factors including HSF-1, NF-κB, CREB and STAT3) and post-transcriptional (via microRNAs including miR-1, miR-21 and miR-24) regulation of HSPs. The cytoprotective nature of HSPs catapults them to the limelight as modulators of cell survival. Yet another attractive prospect is the development of new therapeutic strategies against cardiovascular diseases (from hypertension to heart failure) by targeting the regulation of HSPs. Moreover, this review provides insights into how genetic variation of HSPs can contribute to the manifestation of CVDs. It would also offer a bird's eye view of the evolving role of different HSPs in the modulation and manifestation of cardiovascular disease.