Abstract
Autophagy is a self-degradative pathway by which subcellular elements are broken down intracellularly to maintain cellular homeostasis. Cardiac autophagy commonly decreases with aging and is accompanied by the accumulation of misfolded proteins and dysfunctional organelles, which are undesirable to the cell. Reduction of autophagy over time leads to aging-related cardiac dysfunction and is inversely related to longevity. However, despite the increasing interest in autophagy in cardiac diseases and aging, the process remains an undervalued and disregarded object in calcific valvular disease. Neither the nature through which autophagy is triggered nor the interplay between autophagic machinery and targeted molecules during aortic valve calcification are fully understood. Recently, the upregulation of autophagy has been shown to result in cardioprotective effects against cell death as well as its origin. Here, we review the evidence that shows how autophagy can be both beneficial and detrimental as it pertains to aortic valve calcification in the heart.
Highlights
Calcific aortic valve disease (CAVD) is the most prevalent valvular disease in the elderly and has become a rising social and health burden, especially in developed countries that have an aging baby boomer generation [1]
SIRT6 is a preautophagy histone deacetylase that function in stress response, and SIRT6−/− mice are characterized by cardiac hypertrophy and heart failure [29, 30]
valve interstitial cells (VICs) undergoes osteoblast-phenotype changes upon microenvironment alteration, such as ROS and inflammatory cytokines, with osteogenic nodules observed in the affected leaflets
Summary
Autophagy is responsible for the turnover of abnormal cellular structures and the elimination of microorganisms (bacteria, viruses, and fungi). The autophagosome migrates along microtubules and fuses with lysosomes, leading to the formation of autolysosomes that degrade the vesicular contents This evolutionary, highly conserved process is governed by a succession of molecules, namely autophagy-related genes (ATGs). In the final stage of autophagy, the process of newborn autophagosome fusion with the lysosome is called autophagic degradation or autophagic flux, which leads to the formation of a single membranestructured autolysosome [16, 17] These ATG molecules link ubiquitinated cargoes to the autophagosome and recruit encapsulated cargoes into the autolysosome to degrade through the activity of lysosomal lipases, nucleases, proteases, and glycosidases, and the cell recycles the degraded products for reuse [18]. Autophagy exerts multiple functions through pharmacological and nutritional interventions (Fig. 1) and gives full access to the regulation of cellular metabolism [10, 23, 24]
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