Pharmacological modulation of autophagy during cardiac stress.
Autophagy is an evolutionarily conserved intracellular mechanism for degradation of long-lived proteins and organelles. Accumulating lines of evidence indicate that autophagy is deeply involved in the development of cardiac disease. Autophagy is upregulated in almost all cardiac pathological states, exerting both protective and detrimental functions. Whether autophagy activation is an adaptive or maladaptive mechanism during cardiac stress seems to depend upon the pathological context in which it is upregulated, the extent of its activation, and the signaling mechanisms promoting its enhancement. Pharmacological modulation of autophagy may therefore represent a potential therapeutic strategy to limit myocardial damage during cardiac stress. Several pharmacological agents that are able to modulate autophagy have been identified, such as mammalian target of rapamycin inhibitors, adenosine monophosphate-dependent kinase modulators, sirtuin activators, myo-inositol-1,4,5-triphosphate and calcium-lowering agents, and lysosome inhibitors. Although few of these modulators of autophagy have been directly tested during cardiac stress, many of them seem to have high potential to be efficient in the treatment of cardiac disease. We will discuss the potential usefulness of different pharmacological activators and inhibitors of autophagy in the treatment of cardiac diseases.
Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA.
Sebastiano
S
Sciarretta
Peiyong
P
Zhai
Massimo
M
Volpe
Junichi
J
Sadoshima
D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006331:Heart Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects* / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D015544:Inositol 1,4,5-Trisphosphate; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases