The role of autophagy in cardiac hypertrophy

Abstract

Autophagy is conserved in nature from lower eukaryotes to mammals and is an important self-cannibalizing, degradative process that contributes to the elimination of superfluous materials. Cardiac hypertrophy is primarily characterized by excess protein synthesis, increased cardiomyocyte size, and thickened ventricular walls and is a major risk factor that promotes arrhythmia and heart failure. In recent years, cardiomyocyte autophagy has been considered to play a role in controlling the hypertrophic response. However, the beneficial or aggravating role of cardiomyocyte autophagy in cardiac hypertrophy remains controversial. The exact mechanism of cardiomyocyte autophagy in cardiac hypertrophy requires further study. In this review, we summarize the controversies associated with autophagy in cardiac hypertrophy and provide insights into the role of autophagy in the development of cardiac hypertrophy. We conclude that future studies should emphasize the relationship between autophagy and the different stages of cardiac hypertrophy, as well as the autophagic flux and selective autophagy. Autophagy will be a potential therapeutic target for cardiac hypertrophy.

Soluble epoxide hydrolase inhibitor, TUPS, attenuates isoproterenol/angiotensin II-induced cardiac hypertrophy through mammalian target of rapamycin-mediated autophagy inhibition

“…announced that the inhibition of sEH using UA‐8 promotes cell survival during deep metabolic stresses, such as starvation, because of the activation of autophagy. Several other studies also show that the basal levels of autophagy are essential for homeostasis, and imbalanced levels of autophagy may lead to cardiomyocyte dysfunction or death . Therefore, we speculate that autophagy is a very flexible homeostatic response that could be regulated by specific signalling pathways in response to therapeutic drugs.…”

“…The mTOR signalling pathway negatively regulates autophagy in cardiomyocytes . Conversely, AMPK positively regulates autophagy by inhibiting mTOR signalling . Fan et al .…”

“…Autophagy is an evolutionarily conserved cellular process responsible for the degradation and recycling of unwanted proteins and organelles via a lysosomal‐mediated pathway . The process of autophagy is triggered by a variety of extracellular and intracellular stimuli such as therapeutic agents, glucose starvation, hypoxia and various signalling pathways . Among various cellular signalling pathways, the mammalian target of rapamycin (mTOR) signalling was previously proven to play critical roles in the inhibition of autophagy during myocardial injury .…”

“…Cellular autophagy is also involved in various CVDs including atherosclerosis, myocardial ischaemia–reperfusion injury, heart failure and cardiac hypertrophy . However, the role of autophagy in cardiac hypertrophy remains controversial because of the dual effects of autophagy on cardiac hypertrophy reported previously . Autophagy was observed during the development of cardiac hypertrophy and is promoted by stresses such as transverse aortic constriction (TAC), pulmonary arterial hypertension (PAH) and Ang II .…”

Cannabinoids, the Heart of the Matter

“…It is characterized by a higher rate of protein synthesis, a decrease in size of the heart chamber, and thickening of left and right ventricular walls; as a result, poses as a major risk factor of developing arrhythmia and heart failure 1, 16…”