Autophagy in cardiac metabolic control: Novel mechanisms for cardiovascular disorders

Abstract

As an extensively studied quality control system, autophagy is responsible for clearance of dysfunctional organelles and damaged marcomolecules in cells. In addition to its biological recycling function, autophagy plays a significant role in the pathogenesis of metabolic syndromes such as obesity and diabetes. In particular, metabolic disorders contribute to cardiovascular disease development. As energy required to maintain cardiac cells functional is immense, disturbances in the balance between anabolic and catabolic metabolism possibly contribute to cardiovascular disorders. Therefore, an urgent need to expand our knowledge on the role of autophagy on the metabolic regulation of hearts emerges. In this review, the potential relationship between autophagic activity and cardiac metabolism is explored and we also discuss how dysregulated autophagy leads to severe cardiac disorders from the perspective of metabolic control.

S‐adenosylmethionine: A metabolite critical to the regulation of autophagy

“…Autophagy is also involved in cell death and tumour suppression, 3 neurodegeneration, 4 ageing, 5 inflammation, 6 immunity 7 and genome stability 8 . In addition to starvation, autophagy is induced by many other disturbances, including hypoxia, metabolic disturbances, infiltration and oxidative stresses 9‐12 . Autophagy is regulated by nutrient‐ and energy‐sensing pathways, including the well‐known energy regulators mammalian target of rapamycin (mTOR), AMPK (adenosine 5′‐monophosphate [AMP]–activated protein kinase) and AKT/protein kinase B 13 .…”

“…8 In addition to starvation, autophagy is induced by many other disturbances, including hypoxia, metabolic disturbances, infiltration and oxidative stresses. [9][10][11][12] Autophagy is regulated by nutrient-and energy-sensing pathways, including the wellknown energy regulators mammalian target of rapamycin (mTOR),…”

Activation of CD137 Signaling Enhances Vascular Calcification through c-Jun N-Terminal Kinase-Dependent Disruption of Autophagic Flux

“…In contrast, impaired autophagy contributes to a wide range of vascular pathologies including atherosclerosis and calcification [ 15 , 16 ]. Reactive oxygen species production, oxidized lipoproteins, endoplasmic reticulum stress, and hypoxia are involved in triggering the process of autophagy in atherosclerotic plaques [ 17 – 19 ]. Interestingly, autophagy-associated inflammasomes contribute to atherosclerotic progression [ 20 ].…”