Autophagy in vascular disease.

Abstract

Autophagy is a reparative, life-sustaining process by which cytoplasmic components are sequestered in double-membrane vesicles and degraded on fusion with lysosomal compartments. Growing evidence reveals that basal autophagy is an essential in vivo process mediating proper vascular function. Moreover, autophagy is stimulated by many stress-related stimuli in the arterial wall to protect endothelial cells and smooth muscle cells against cell death and the initiation of vascular disease, in particular atherosclerosis. Basal autophagy is atheroprotective during early atherosclerosis but becomes dysfunctional in advanced atherosclerotic plaques. Little is known about autophagy in other vascular disorders, such as aneurysm formation, arterial aging, vascular stiffness, and chronic venous disease, even though autophagy is often impaired. This finding highlights the need for pharmacological interventions with compounds that stimulate the prosurvival effects of autophagy in the vasculature. A large number of animal studies and clinical trials have indicated that oral or stent-based delivery of the autophagy inducer rapamycin or derivatives thereof, collectively known as rapalogs, effectively inhibit the basic mechanisms that control growth and destabilization of atherosclerotic plaques. Other autophagy-inducing drugs, such as spermidine or add-on therapy with widely used antiatherogenic compounds, including statins and metformin, are potentially useful to prevent vascular disease with minimal adverse effects.

• Authors: Guido R Y De Meyer, Mandy O J Grootaert, Cédéric F Michiels, Ammar Kurdi, Dorien M Schrijvers, Wim Martinet
• Journal: Circulation research (Circ Res) Vol. 116 Issue 3 Pg. 468-79 (Jan 30 2015) ISSN: 1524-4571 [Electronic] United States
• PMID: 25634970 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2015 American Heart Association, Inc.

Topics

• Animals
• Autophagy
• Endothelium, Vascular (metabolism)
• Humans
• Muscle, Smooth, Vascular (metabolism)
• Vascular Diseases (metabolism, pathology)