Oxygen Sensing, Cardiac Ischemia, HIF-1α and Some Emerging Concepts

Abstract

Oxygen plays a critical role in the perpetuation and propagation of almost all forms of life. The primary site of cellular oxygen consumption is the mitochondrial electron transport chain and in addition, oxygen is also used as a substrate for various enzymes involved in cellular homeostasis. Although our knowledge of the biochemistry and physiology of oxygen transport is century old, recent development of sophisticated tools of biophysical chemistry revealed that tissue oxygenation and oxygen sensing is a highly evolved process, especially in mammals. Perturbation of normal oxygen supply is associated with diseases like tumorigenesis, myocardial infarction and stroke. Available information suggests that when tissue oxygen supply is limited, mitochondria emanate signals involving reactive oxygen species generation which in turn stabilizes oxygen sensing transcription factor HIF-1. Upon stabilization, HIF-1 elicits necessary genetic response to cope with the diminished oxygen level. In view of such critical role of HIF-1 in cellular oxygen sensing, recently there has been a heightened interest in understanding the biology of HIF-1 in the context of cardiovascular system. The following review describes some of the recent advances in this regard.