Molecular Mechanisms of Autophagy in the Cardiovascular System

Abstract

Autophagy is a catabolic recycling pathway triggered by various intra- or extracellular stimuli that is conserved from yeast to mammals. During autophagy diverse cytosolic constituents are enveloped by double-membrane vesicles, autophagosomes, which later fuse with lysosomes or the vacuole in order to degrade their cargo. Dysregulation in autophagy is associated with a diverse range of pathologies including cardiovascular disease, the leading cause of death in the world. As such, there is great interest in identifying novel mechanisms that govern the cardiovascular response to disease-related stress. First described in failing hearts, autophagy within the cardiovascular system has been widely characterized in cardiomyocytes, cardiac fibroblasts, endothelial cells and vascular smooth muscle cells. In all cases, a window of optimal autophagic activity appears to be critical to the maintenance of cardiovascular homeostasis and function; excessive or insufficient levels of autophagic flux can each contribute to heart disease pathogenesis. Here we review the molecular mechanisms that govern autophagosome formation and analyze the link between autophagy and cardiovascular disease.

Bcl-2–associated athanogene 3 protects the heart from ischemia/reperfusion injury

“…The role of autophagy (25,26) and apoptosis (27,28) in the development of cardiovascular disease and in particular in the development of heart failure has been well recognized and is the subject of recent reviews. In fact, modest overexpression of active caspase leads to the development of heart failure (28).…”

Cardiac mTOR rescues the detrimental effects of diet-induced obesity in the heart after ischemia-reperfusion

“…Autophagy is a catabolic cellular process mediated by lysosomes and plays an important role in cellular homeostasis in many organs, including the heart (14,29). The mTORC1 axis is a potential antiautophagic response that regulates the UNC-51-like kinase complex (14).…”

“…However, since phosphorylation levels of both S6 and Akt in hearts after I/R were high, especially in HFD conditions, it was difficult to identify whether mTOR overexpression made a difference in activation between mTORC1 and mTORC2 after I/R. mTORC1 suppresses autophagy in the mTOR signaling pathway (14). Dysregulation of autophagic flux is known as a key pathogenic factor in cardiac diseases, including I/R injury and diet-induced obesity (29,55).…”

Protective effects of luteolin-7-O-glucoside against starvation-induced injury through upregulation of autophagy in H9c2 Cells

“…In response to starvation, autophagy is upregulated that provides an internal source of nutrients for energy generation and, thus promotes survival (3,4). Autophagy is a process of self-cannibalization in which doublemembrane autophagosomes sequester organelles or portions of cytosol and fuse with lysosomes for breakdown by resident hydrolases (5,6). The resulting breakdown products can be recycled back to the cytosol for reuse during starvation, and are used to generate energy and to build new proteins and membranes (5,6).…”

“…Autophagy is a process of self-cannibalization in which doublemembrane autophagosomes sequester organelles or portions of cytosol and fuse with lysosomes for breakdown by resident hydrolases (5,6). The resulting breakdown products can be recycled back to the cytosol for reuse during starvation, and are used to generate energy and to build new proteins and membranes (5,6). Autophagy may function primarily as a cytoprotective mechanism, to maintain nutrient and energy homeostasis during starvation conditions (7,8).…”