The Protective Effects of the Autophagic and Lysosomal Machinery in Vascular and Valvular Calcification: A Systematic Review

Abstract

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.

Decreased monocyte calcium sensing receptor expression in patients with chronic kidney disease is associated with impaired monocyte ability to reduce vascular calcification

“…37 The activation of the lysosomal system is consistent with an antimineralizing process. 38 Although it is currently admitted that dysregulated or inappropriate environmental stimuli, including aging, atherosclerosis, CKD, diabetes, and chronic inflammatory diseases, such as rheumatoid arthritis, in association with dysregulations of calcium and phosphate homeostasis are involved in the initiation and the development of vascular calcifications, it seems unlikely that monocytes will be affected similarly by these pathologic conditions. Therefore, further exploration of circulating monocyte "antimineralizing" capacities in various procalcifying conditions will be needed to decipher the exact role played by monocytes and CaSR activation in this process.…”

Insights Into the Role of Mitochondria in Vascular Calcification

“…Autophagy is an important means for the maintenance of intracellular homeostasis; mitophagy is a subtype of autophagy that is considered as a protective mechanism to clear the damaged or unnecessary mitochondria, and normal mitophagy also highlights a critical role in maintaining mitochondrial biogenesis (146,147). Altered mitophagic flux by pharmacological or genetic maneuvers has been shown to influence the VC process (148). The main mechanism may be related to the reduction of ROS release and mitochondrial-related apoptosis.…”

Inflammation, Nitro-Oxidative Stress, Impaired Autophagy, and Insulin Resistance as a Mechanistic Convergence Between Arterial Stiffness and Alzheimer’s Disease

“…Similar to osteoblasts, VSMCs are able to undergo osteogenic differentiation when exposed to increased intracellular concentrations of calcium and/or inorganic phosphate ( Neutel et al, 2020 ). Overexpression of calpain-1 reduces the calcification inhibitors such as osteopontin and osteonectin ( Jiang et al, 2012 ; Tang et al, 2015 ).…”