doi: 10.1161/CIRCRESAHA.108.175562
© 2008 American Heart Association, Inc.
Editorials |
Living on the Edge
Hypoxia-Induced Tissue Damage
From the Klinik III für Innere Medizin, and Center for Molecular Medicine Cologne, Universität zu Köln, Germany.
Correspondence to Evren Caglayan, MD, Klinik III für Innere Medizin, Universität zu Köln, Kerpener Str. 62, D-50937 Köln, Germany. E-mail evren.caglayan@uk-koeln.de
See related article, pages 905–913
Key Words: AGE • hypoxia • RAGE • egr-1
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
How a seemingly simple signal (ie, hypoxia) becomes transduced into biochemical and molecular responses that mediate maladaptive tissue damage is the defining enigma in various events that lead to oxygen deprivation, such as myocardial infarction, stroke, and venous thromboembolism. It is well established that acute hypoxia leads to numerous cellular events, such as formation of reactive oxygen species and induction of hypoxia-inducible factor-1.1 Furthermore, the immediate early gene, early growth response (Egr)-1, appears as an integral component of the biological response to hypoxia,2 because its upregulation induces the expression of fundamental inflammatory and prothrombotic stress genes.3 Nevertheless, the exact role of the above molecules and the link between hypoxia and Egr-1 upregulation/inflammation remains elusive. It is certainly desirable to better characterize the molecular basis of hypoxic cellular injury to develop pathway-specific therapeutic strategies to limit hypoxia-induced tissue damage in various organs such as the heart, brain, and vasculature.
Formation of advanced glycation end products (AGEs) are implicated in the pathogenesis of diabetic micro- and macrovascular complications, resulting in diabetic heart disease, accelerated atherosclerosis, end-stage renal failure, a variety of neuropathies, and acquired blindness.4 For several years, it has been known that high blood glucose concentrations promote AGE formation inside and outside cells.5 In addition, there is increasing evidence that AGE formation also occurs independent of plasma glucose levels. For example, oxidants generated by the NADPH oxidase of neutrophils, monocytes, and macrophages may also play a role in AGE formation in vivo by a glucose-independent pathway.6
The interaction of glucose-modified and
Related Article:
Circ. Res. 2008 102: 905-913.