W i l f r i e d R e n n e r, G e r a l d Wo l f , M a r t i e Tr u s c h n i g , U w e L a n g s e n l e h n e r, P e t e r K r i p p l
Molekulare Mechanismen der Höhenanpassung und ihre mögliche klinische Bedeutung Molecular mechanisms of adaptation to high altitude and their potential clinical implication S U M M A RY The lower amount of oxygen in the atmosphere at high altitude (hypoxia) leads to a row of adaptation processes in the body, such as sensitizing of breath activity, an expression and activation of hormones Vascular Endothelial Growth Factor (VEGF), Hypoxia-inducible factor 1 (HIF-1) and Erythropoietin (Epo). VEGF is a signal molecule which has an important function in the vasculogenesis (de novo formation of the the embryonic vascular system) and angiogenesis (development of additional vessels to the existing vascular system). VEGF plays furthermore an important role in the vascularisation of tumors and development of metastases. Elevated VEGF levels have been associated with a worse prediction of different tumors in a variety of studies. A rather fast adaptation to high altitude is mediated by Epo, which stimulates the formation of red blood cells in the bone marrow. Recombinant Epo is used in patients with anemia. The expression of VEGF and Epo is regulated by HIF-1, which plays a key role in response to hypoxia, including the regulation of up to 100 different genes. Recently, HIF-1 stabilizers have been tested as a new therapy option for a variety of diseases. Since HIF-1 is known to be an essential factor for the development and growth of tumors, the application of HIF-1 stabilizers might lead to serious unwanted side-effects in cancer patients. The safety of HIF-1 stabilizers is currently tested in clinical studies. Keywords: High altitude hypoxia, HIF-1, VEGF, erythropoietin, gene expression.
Z U S A M M E N FA S S U N G Das mit einem Aufenthalt in der Höhe einhergehende verringerte Sauerstoffangebot in der Umgebungsluft (Hypoxie) führt im Organismus zu einer Reihe von Anpassungsprozessen, wie eine Sensibilisierung der Atemtätigkeit sowie die
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