The Role of Autophagy and Potential Drug Targets in Cardiovascular Disease

Abstract

Autophagy is integral in the protection and survival of cardiomyocytes in heart disease. If impaired, it can lead to apoptosis of healthy cardiac tissue. This review discusses the role of autophagy in heart disease. Primary mechanisms and their benefits for cellular homeostasis in cardiomyocytes will be explored as well as the effects of dysregulated autophagy on aggravating conditions and the potential therapeutic approaches to modulate autophagy to improve outcomes in heart disease. Autophagy degrades damaged cellular components during myocardial infarction, increasing energy levels to reduce Ischemic/Reperfusion injury. However, over-activation of autophagy can contribute to this injury by forming excessive autophagosomes, which destabilize mitochondria, consequently accelerating cell apoptosis and cardiac injury. In atherosclerosis, disrupted autophagy promotes cell apoptosis, exacerbating inflammation and worsening atherogenesis. In contrast, tightly regulated autophagy promotes cell survival in vascular smooth muscle cells. Autophagy helps adaptively remodel the heart and compensate for cardiac overload. Abnormal levels of autophagy can increase the progression of cardiac hypertrophy to heart failure by degrading crucial cellular components. Autophagy plays various roles in many heart diseases, making it a promising target in developing new therapies to recover and minimize heart disease damage. When exploring pharmacological treatments for diabetic cardiomyopathy, a large percentage are autophagy modulators, which have the potential to be utilized to promote cardiac repair in cardiovascular disease.