MIA3 in Coronary Artery Disease (CAD): An In-Depth Review of Its Role in Vascular Smooth Muscle Cell (VSMC) Homeostasis, Pathogenesis, and Its Therapeutic Potential

Abstract

A significant portion of fatalities from coronary artery disease (CAD) has been attributed to be primarily triggered by atherosclerosis. The melanoma inhibitory activity protein-3 (MIA3) gene has been found to be a key regulator for plaque stability in coronary artery atherosclerosis. Recent advances have unveiled the role of this gene in the formation of MIA3 protein, via which it potentially regulates the homeostatic circuit of various molecular proteins inside the cell and provides a safety profile to heart patients. Understanding how this gene exists, functions, signals, and can be targeted is therefore crucial to tackle the challenges in the field of cardiology. In this review, we have elaborated on its role in various cellular processes and several reported diseases to develop a holistic insight into the function of this gene. We have shown how this gene contributes to the budding of vesicles from the endoplasmic reticulum and helps in the transport of apolipoproteins and collagen to the exterior of the cell. We shed light on its role in the pathogenesis of CAD and also explain its role in other diseases involving bone mineralization or collagen defects. We explore the MIA3 gene at both genetic and protein levels and elaborate on its evolutionary conservation across species. In this paper, we also dissect the signaling mechanisms of the MIA3 gene inside the cell involving several protein interactions to form the COPII complex and initiate the vesicular budding at the endoplasmic reticulum. We also discuss the various therapeutic options that can target the MIA3 signaling pathway in several diseases, with a particular emphasis on CAD.