Role of autophagy in advanced atherosclerosis

Abstract

Abstract. Atherosclerosis (AS) remains the leading cause for global cardiovascular disease morbidity and mortality, and a major cause of cardiopathy, myocardial infarction and peripheral vascular diseases. Macrophages serve a critical role in atherosclerotic plaque stabilization and rupture, and the selective removal of macrophages may be beneficial in improving plaque stability. Autophagy is a process of self-feeding, during which cytoplasmic proteins or organelles are packaged into vesicles and fused with the lysosome to form an autophagosome. The newly formed autophagosome can degrade internalized proteins, and this process may be used to serve the metabolic and self-renewal requirements of the cell. Autophagy serves an important role in maintaining cell homeostasis and promoting cell survival, and therefore an imbalance in autophagy is closely associated with multiple diseases. Contents1. Introduction 2. The molecular mechanism of autophagy 3. Autophagy in the vascular system 4. Autophagy in AS 5. Conclusions IntroductionAutophagy is a process of cellular repair and survival, during which cytoplasmic components are sequestered into double-membrane vesicles. Previous research has revealed that autophagy is stimulated in advanced atherosclerotic plaques by oxidized lipids, inflammation and metabolic stress (1). Autophagy is beneficial in promoting cellular recovery in adverse environments; it is also valuable in inhibiting apoptosis. In advanced atherosclerosis (AS), macrophage apoptosis, together with defective phagocytic clearance of the apoptotic cells, promotes plaque necrosis, which results in acute atherothrombotic cardiovascular events (2). Basal autophagy is beneficial in early AS, however a detrimental effect is observed in advanced AS plaques (3); autophagy is capable of protecting cells from oxidative stress via the degradation of damaged intracellular material; however, excessively stimulated autophagic activity may result in significant destruction of the cytosol (1). The latter scenario leads to programmed cell death and may cause vascular endothelial cell (VEC) death, which results in plaque destabilization. Endothelial injury or death represents a predominant mechanism of acute clinical events, due to the promotion of lesional thromboses (4). Furthermore, insufficient autophagic activity also reduces free cholesterol and apolipoprotein A-I (5), and this decreases the amount of high-density lipoprotein. Insufficient and excessive autophagy of VECs are therefore both injurious, and the regulation of autophagic homeostasis may be important in the treatment of AS. The molecular mechanism of autophagyWhen Ashford and Porter (6) perfused rat livers with glucagon, they discovered a large increase in the number of cellular lysosomes. This phenomenon of self-feeding was referred to as autophagy. This process involves the packaging of cytoplasmic proteins or organelles into vesicles, followed by lysosomal fusion, to form an autophagic lysosome; a cellular event which aids in metabolism and in the renewal...

Programmed cell death protein 4 deficiency suppresses foam cell formation by activating autophagy in advanced glycation end‐product low‐density lipoprotein–induced macrophages

“…6 Mounting evidence have indicated that autophagy has a promising potential as diagnostic and prognostic indicators in various diseases containing atherosclerosis. 7 Lipoautophagy, a type of autophagy that delivers lipid droplets (LDs) for degradation and regulates lipid metabolism, is involved in the process of atherosclerosis. 8 Activation of autophagy by intercellular and/or extracellular stimuli protects macrophage cells against cell apoptosis.…”

“…Autophagy is an evolutionary conserved metabolic process in which denatured proteins and damaged organelles are degraded through the lysosomal system for the maintenance of intracellular homeostasis during various stress conditions . Mounting evidence have indicated that autophagy has a promising potential as diagnostic and prognostic indicators in various diseases containing atherosclerosis . Lipoautophagy, a type of autophagy that delivers lipid droplets (LDs) for degradation and regulates lipid metabolism, is involved in the process of atherosclerosis .…”

BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque

“…In fact, autophagy is involved in multiple processes of carotid plaque formation and differentiation, and may constitute a protective mechanism to promote cell survival in the plaque [29,37]. Current research indicates that autophagy becomes dysfunctional during the progression of atherosclerosis, and that this process affects the main cellular constituents of the plaque differently [38,39]. Plaque-associated macrophages respond to autophagy impairment by undergoing apoptosis, while VSMCs engage the senescence program, with both phenomena shown to promote plaque progression [39].…”

Fatty Acid Binding Protein-4 Silencing Attenuates Atherosclerosis Progression by Affecting Macrophage Apoptosis and Autophagy

“…Previous study has reported that plaque necrosis in advanced atherosclerosis might be due to the defects in clearing apoptotic macrophage cells which results in atherosclerotic cardiovascular events [27]. Autophagy is another biologically conservative process that plays an important role in maintaining lipid metabolism and apoptosis in obesity and atherosclerosis.…”