The Role of Oxygen Sensors, Hydroxylases, and HIF in Cardiac Function and Disease.
Ischemic heart disease is the leading cause of death worldwide. Oxygen-sensing proteins are critical components of the physiological response to hypoxia and reperfusion injury, but the role of oxygen and oxygen-mediated effects is complex in that they can be cardioprotective or deleterious to the cardiac tissue. Over 200 oxygen-sensing proteins mediate the effects of oxygen tension and use oxygen as a substrate for posttranslational modification of other proteins. Hydroxylases are an essential component of these oxygen-sensing proteins. While a major role of hydroxylases is regulating the transcription factor HIF, we investigate the increasing scope of hydroxylase substrates. This review discusses the importance of oxygen-mediated effects in the heart as well as how the field of oxygen-sensing proteins is expanding, providing a more complete picture into how these enzymes play a multifaceted role in cardiac function and disease. We also review how oxygen-sensing proteins and hydroxylase function could prove to be invaluable in drug design and therapeutic targets for heart disease.
Department of Medicine, Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA.
W H Davin
WH
Townley-Tilson
Department of Medicine, Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Xinchun
X
Pi
Department of Medicine, Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Liang
L
Xie
D006321:Heart / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D006899:Mixed Function Oxygenases; D010100:Oxygen