Autophagy in the cardiovascular system.
Autophagy is a catabolic pathway for bulk turnover of long-lived proteins and organelles via lysosomal degradation. Growing evidence reveals that autophagy is involved in the progression or prevention of many human diseases. Here we discuss the role of autophagy in the normal heart, in heart disease and atherosclerosis. In the heart, autophagy functions predominantly as a pro-survival pathway during cellular stress by removing protein aggregates and damaged organelles, protecting the heart against famine, excessive beta-adrenergic stimulation and ischemia. However, when severely triggered, e.g. during reperfusion, the autophagic machinery may lead to cell death. Furthermore, autophagy modulates cardiac hypertrophy and the transition from hypertrophy to heart failure. During aging, lipofuscin is formed via autophagy in the heart and impairs autophagy. Basal autophagy in atherosclerotic plaques is a survival mechanism safeguarding plaque cells against cellular distress, in particular oxidative injury, metabolic stress and inflammation, by removing harmful oxidatively modified proteins and damaged components. Hence, autophagy is anti-apoptotic and contributes to cellular recovery in an adverse environment. However, excessively stimulated autophagy causes autophagic death in plaque cells and is detrimental. Ceroid that is formed via autophagy in atherosclerotic arteries impairs autophagy and induces apoptosis. Basal autophagy can be intensified by appropriate drugs and pharmacological approaches have been developed to stabilize rupture-prone plaques through selective induction of macrophage autophagic death, without affecting the plaque stabilizing smooth muscle cells.
De Meyer
Guido R Y
GR
Division of Pharmacology, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium. guido.demeyer@ua.ac.be
Martinet
Wim
W
D000818:Animals; D001343:Autophagy; D002318:Cardiovascular Diseases / Q000473:pathology; D002319:Cardiovascular System / Q000166:cytology*; D006801:Humans; D009206:Myocardium / Q000166:cytology