The Protective Effects of the Autophagic and Lysosomal Machinery in Vascular and Valvular Calcification: A Systematic Review.
BACKGROUND
Autophagy is a highly conserved catabolic homeostatic process, crucial for cell survival. It has been shown that autophagy can modulate different cardiovascular pathologies, including vascular calcification (VCN).


OBJECTIVE
To assess how modulation of autophagy, either through induction or inhibition, affects vascular and valvular calcification and to determine the therapeutic applicability of inducing autophagy.


DATA SOURCES
A systematic review of English language articles using MEDLINE/PubMed, Web of Science (WoS) and the Cochrane library. The search terms included autophagy, autolysosome, mitophagy, endoplasmic reticulum (ER)-phagy, lysosomal, calcification and calcinosis. Study characteristics: Thirty-seven articles were selected based on pre-defined eligibility criteria. Thirty-three studies (89%) studied vascular smooth muscle cell (VSMC) calcification of which 27 (82%) studies investigated autophagy and six (18%) studies lysosomal function in VCN. Four studies (11%) studied aortic valve calcification (AVCN). Thirty-four studies were published in the time period 2015-2020 (92%).


CONCLUSION
There is compelling evidence that both autophagy and lysosomal function are critical regulators of VCN, which opens new perspectives for treatment strategies. However, there are still challenges to overcome, such as the development of more selective pharmacological agents and standardization of methods to measure autophagic flux.
['Neutel|Cédric H G|CHG|0000-0001-7074-226X', 'Hendrickx|Jhana O|JO|0000-0001-7639-2926', 'Martinet|Wim|W|', 'De Meyer|Guido R Y|GRY|0000-0003-3848-8702', 'Guns|Pieter-Jan|PJ|0000-0002-8640-6620']
D001021:Aortic Valve D001024:Aortic Valve Stenosis D001343:Autophagy D002114:Calcinosis D002470:Cell Survival D004721:Endoplasmic Reticulum D006801:Humans D008247:Lysosomes D009131:Muscle, Smooth, Vascular D032389:Myocytes, Smooth Muscle D061205:Vascular Calcification
lysosomes autophagy vascular calcification vascular smooth muscle cell (VSMC) aortic valve calcification valvular interstitial cell (VIC)