Physical Exercise and Selective Autophagy: Benefit and Risk on Cardiovascular Health

Abstract

Physical exercise promotes cardiorespiratory fitness, and is considered the mainstream of non-pharmacological therapies along with lifestyle modification for various chronic diseases, in particular cardiovascular diseases. Physical exercise may positively affect various cardiovascular risk factors including body weight, blood pressure, insulin sensitivity, lipid and glucose metabolism, heart function, endothelial function, and body fat composition. With the ever-rising prevalence of obesity and other types of metabolic diseases, as well as sedentary lifestyle, regular exercise of moderate intensity has been indicated to benefit cardiovascular health and reduce overall disease mortality. Exercise offers a wide cadre of favorable responses in the cardiovascular system such as improved dynamics of the cardiovascular system, reduced prevalence of coronary heart diseases and cardiomyopathies, enhanced cardiac reserve capacity, and autonomic regulation. Ample clinical and experimental evidence has indicated an emerging role for autophagy, a conservative catabolism process to degrade and recycle cellular organelles and nutrients, in exercise training-offered cardiovascular benefits. Regular physical exercise as a unique form of physiological stress is capable of triggering adaptation while autophagy in particular selective autophagy seems to be permissive to such cardiovascular adaptation. Here in this mini-review, we will summarize the role for autophagy in particular mitochondrial selective autophagy namely mitophagy in the benefit versus risk of physical exercise on cardiovascular function.

Keywords: autophagy; benefit; cardiovascular; physical exercise; risk; selective autophagy.

Figure 1

Schematic of mitochondrial adaptations in response to exercise and how it contributes to cardioprotection.

Figure 2

Mechanism and signaling pathways involved in mitochondrial adaptation in heart following exercise. Acute exercise augments mitophagy depending on the phosphorylation of AMPK (protein kinase AMP-activated catalytic subunit alpha 1) and ULK1 (unc-51 like autophagy activating kinase 1). AMPK could be activated by exercise-related increase of AMP/ATP ratio, sympathetic activation and other signaling. Mitophagy removes dysfunctional mitochondria and reduces reactive oxygen species (ROS). AMPK also promotes mitochondrial biogenesis through regulating PGC-1a. Regular exercise mainly activates the IGF1-PI3K-Akt pathway, which targets several transcription factors in nucleus and contributes to cell growth, cellular survival, metabolic homeostasis, and mitochondrial maintenance. Abbreviations: AMPK, AMP-activated kinase; Sirt1, Sirtuin 1; PGC-1a, peroxisome proliferator activated receptor gamma co-activator 1a; IGF-1, insulin-like growth factor-1; PI3K, phosphoinositide-3 kinase; Akt, serine/threonine-protein kinase; C/EBPβ, CCAAT/enhancer binding protein b; Cited4, cbp/p300- interacting transactivator with Glu/Asp-rich carboxy-terminal domain 4; SRF, serum response factor.