The Role of Stress Granules in Cardiovascular Diseases

Recent research has highlighted the pivotal role of RNA metabolism-related stress responses in the pathophysiology of cardiovascular diseases, particularly atherosclerosis, stroke, atrial fibrillation (AF), and heart failure (HF). Stress granules (SGs) are dynamic, membraneless organelles that arise during RNA metabolism via liquid-liquid phase separation (LLPS), in which mRNA associates with RNA-binding proteins (RBPs). SGs form following translation arrest in response to various external stimuli, resulting in cytoplasmic accumulation of mRNA and RBPs, which subsequently aggregate into membraneless messenger ribonucleoprotein (mRNP) granules, including Cajal bodies, SGs, P bodies, RNA transport granules, and germinal bodies. This review focuses specifically on SGs. SG formation is typically a transient and protective cellular response to stress; however, the dysregulation or persistence of SG formation has been implicated in a range of diseases, including cardiovascular conditions, neurodegenerative disorders, cancers, immune responses, and viral infections. Thus, this review examines the physiology and pathology of SGs, detailing the associated formation, composition, regulation, and function, with a particular focus on the involvement of SGs in cardiovascular diseases (CVDs) and potential therapeutic strategies targeting SGs. Moreover, this review outlines the complete life cycle of SGs and the associated implications in CVD. SGs originate near the endoplasmic reticulum (ER) and mitigate apoptosis by curbing mitochondrial production of reactive oxygen species. SGs can also disrupt the trafficking of specific cargo from the ER to the Golgi apparatus. Furthermore, SGs can repair damaged lysosomes and eventually undergo self-clearance via the autophagy-lysosome pathway. This model provides new perspectives for researchers in cardiovascular medicine, physicians, and translational medical researchers, and may advance our understanding of SG-related pathophysiology and facilitate the identification of novel therapeutic targets for CVDs.