Special Topic on the Many Faces of Hypoxia

Each year High Altitude Medicine & Biology selects a Special Topic for one issue. This year's topic was prompted by a report by Max Gassmann in the March 2012 issue of a meeting in La Verité, Switzerland that included discussions of recent research on the great variety of physiological consequences of oxygen deprivation. Dr. Gassmann was invited to select four of the most interesting areas to be this issue's Special Topic.

It was only a few years ago that an article on the physiological effects of high altitude hypoxia was essentially limited to a discussion of hyperventilation, polycythemia, pulmonary hypertension, and possibly a few words about the increased concentration of capillaries in skeletal muscle, and changes of oxidative enzymes within cells. Indeed many medical textbooks still limit their treatment to these areas. However the discovery of hypoxia inducible factors (HIFs) by Semenza and colleagues has resulted in a revolution in high altitude biology. HIFs are transcription regulators that respond to hypoxia by either increasing the rate of gene transcription, that is upregulation, or decreasing the rate of gene transcription, that is downregulation. As a result, in cellular hypoxia the transcription of several hundred mRNAs is increased, and the transcription of a large number is decreased. This Special Topic is devoted to just four of the new areas where hypoxia is critical: the blood-brain barrier, the fate of stem cells, the eye, and the placenta.

The recognition of the multitude of effects of HIFs is responsible for a sea-change in research in high altitude biology. This issue introduces the reader to a few of the contributions in this area.