Recent Advances in Cardiometabolic Diseases: The Therapeutic Implication of Cardiac Exosomes

Abstract

Background: Cardiometabolic diseases (CMD) and its complications have reached epidemic proportions worldwide. These metabolic diseases and related syndrome such as type 2 diabetes mellitus, obesity, and metabolic-associated steatotic liver disease, among others account for the rising in cardiac morbidity and mortality worldwide. Considering the excruciating burden of CVDs globally, and the possible therapeutic potential of exosomes, the present review is undertaken to provide information regarding the current advances in CMDs and its complications.

Discussion: Result from the present findings showed that exosomal miRNAs (miR-103, miR-29, and miR-107) regulate hepatic gluconeogenesis, insulin secretion, and autophagy, impacting glucose metabolism. Additionally, exosomes enhance local and ischemic inflammation by stimulating inflammatory cytokine release from immune and endothelial cells in plaque formation. Furthermore, exosomes contribute to endothelial dysfunction by reducing nitric oxide production, thereby altering vascular tone, and promoting plaque formation. They also facilitate lesion progression, vascular calcification, and endothelial rupture. Exosomal non-coding RNAs (miR-1 and miR-133a) are also implicated in cardiac remodelling and fibrosis. However, the findings also revealed that exosomes from healthy cardiac fibroblasts protect cardiomyocytes from ischemic injury by enhancing miR-423-3p, which downregulates RAP2C, reducing apoptosis. Similarly, exosomes from healthy cardiomyocytes of subjects interact via activating pathways (TLR4, ERK, p38MAPK, HSP27, HSP70) that inhibit apoptosis.

Conclusion: This review showed that extracellular vesicles, exosome played a pivotal role in the CMD, which suggests that exosomes could be a possible therapeutic target in ameliorating CMD and CVD risk.