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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:525.)
© 2002 American Heart Association, Inc.

Editorials

When Sleeping Beauty Turns Ugly

Mitochondria in Hypoxia

Ascan Warnholtz; Maria Wendt; Thomas Münzel

From The University Hospital Eppendorf, Division of Cardiology, Hamburg, Germany.

Correspondence to Thomas Munzel, MD, Universitätskrankenhaus Eppendorf, Abteilung für Kardiologie, Martinistraße 52, 20246 Hamburg, Germany. E-mail muenzel@uke.uni-hamburg.de

During the past 2 decades, it has become evident not only that the vascular endothelium is a physical barrier separating blood flow from the underlying vessel wall but also that it plays a crucial role in maintaining intravascular and extravascular homeostasis. Under physiological conditions, the endothelium works in concert with other vessel wall cells to maintain a balance in the regulation of vascular tone, cell growth, coagulation, leukocyte adhesion and migration and the production of cytokines or other paracrine signaling molecules. Endothelial cells, as eukaryotic cells in general, are dependent on aerobic metabolism, inasmuch as mitochondrial respiration offers greater efficiency for the extraction of energy charge from glucose than does anaerobic glycolysis. Importantly, reduction of tissue oxygen tension, as seen in hypoxia, is a common factor in many diseases, including pulmonary disorders, occlusive vascular disease, and septic shock (conditions in which the arterial blood supply becomes compromised).

See page 566

Although endothelial cells have developed protective mechanisms to withstand ischemic challenge, severe hypoxia has been found to trigger profound changes in endothelial phenotype, leading to a state of endothelial activation that may turn into an uncontrolled state of endothelial dysfunction. Dysfunctional endothelium is characterized by altered vascular homeostasis, disrupted homeostatic balance in coagulation, increased vascular permeability, and increased vascular tone. Subsequent microcirculatory failure and local inflammation may ultimately lead to end-organ damage in the setting of hypoxia.

Important mechanisms of hypoxia-induced vascular dysfunction include increased vasoconstriction due to enhanced endothelin-1 production¹ or ACE expression, ² decreased NO synthase III expression,³ decreased . . . [Full Text of this Article]

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