title: Therapeutic targeting of autophagy: potential and concerns in treating cardiovascular disease.
abstract: Autophagy is an evolutionarily conserved process by which long-lived proteins and organelles are sequestered by autophagosomes and subsequently degraded by lysosomes for recycling. Autophagy is important for maintaining cardiac homeostasis and is a survival mechanism that is upregulated during stress or starvation. Accumulating evidence suggests that dysregulated or reduced autophagy is associated with heart failure and aging. Thus, modulating autophagy represents an attractive future therapeutic target for treating cardiovascular disease. Activation of autophagy is generally considered to be cardioprotective, whereas excessive autophagy can lead to cell death and cardiac atrophy. It is important to understand how autophagy is regulated to identify ideal therapeutic targets for treating disease. Here, we discuss the key proteins in the core autophagy machinery and describe upstream regulators that respond to extracellular and intracellular signals to tightly coordinate autophagic activity. We review various genetic and pharmacological studies that demonstrate the important role of autophagy in the heart and consider the advantages and limitations of approaches that modulate autophagy.
authors: From the Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla.
authors: Amabel M
authors: AM
authors: Orogo
authors: From the Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla. asag@ucsd.edu.
authors: Åsa B
authors: ÅB
authors: Gustafsson
mesh_terms: D000818:Animals; D001343:Autophagy; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D015398:Signal Transduction
keywords: autophagy; heart failure; mitochondria
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