Copyright © 2006, European Society of Cardiology
Perceived hyperoxia: Oxygen-induced remodeling of the reoxygenated heart
Laboratory of Molecular Medicine, 512 Davis Heart and Lung Research Institute, Department of Surgery, The Ohio State University Medical Center, 473 W. 12th Avenue, Columbus, OH 43210, United States
* Corresponding author. Tel.: +1 614 247 7658; fax: +1 614 247 7818. Email address: chandan.sen{at}osumc.edu
Focal coronary artery blockage followed by further reperfusion injury is commonly involved in myocardial infarction. The injured heart has some inherent reparative responses. Although such natural healing mechanisms seem to be inefficient, a clear understanding of the underlying principles of myocardial healing holds the key to successful therapy. Under normoxic conditions, pO2 ranges from 90 to <3 Torr in mammalian organs with the heart at 
35 Torr (5%) and arterial blood at 100 Torr. Thus, "normoxia" for cells is an adjustable variable. In response to chronic moderate hypoxia, cells lower their normoxia set-point such that reoxygenation-dependent relative elevation of pO2 (+
pO2) results in perceived hyperoxia. Perceived hyperoxia induces differentiation of cardiac fibroblasts to myofibroblasts in the peri-infarct region and represents a significant factor supporting myocardial healing. The oxygen-sensitive signaling pathways involved have been characterized and point towards a central role of p21, TGFβ and p38MAPK. That low oxygen ambience serves as a cue to trigger angiogenesis is a well-accepted notion. Studies related to perceived hyperoxia establish that the sensing of oxygen environment is not limited to hypoxia. It demonstrates that in addition to being a trigger for injury as is widely recognized, reoxygenation insult has a built-in component of tissue remodeling in the peri-infarct region induced by perceived hyperoxia. Understanding of the underlying mechanisms of this and other myocardial healing responses should prove to be instrumental in developing productive therapeutic approaches to mend the infarcted heart.
KEYWORDS Cardiac fibroblast; Myofibroblast; Reoxygenation; Healing
Time for primary review 40 days
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