Effect of Intermittent High Altitude Hypoxia on Gene
Expression in Rat Heart and Lung
E. DEINDL, F. KOLÁŘ1, E. NEUBAUER,
S. VOGEL, W. SCHAPER, B. OŠŤÁDAL1
Department of Experimental Cardiology, Max-Planck-Institute
for Physiological and Clinical Research, W. G. Kerckhoff
Institute, Bad Nauheim, Germany and 1Institute
of Physiology, Academy of Sciences of the Czech Republic
and Center for Experimental Cardiovascular Research,
Prague, Czech Republic
Received March 8, 2002
Accepted June 6, 2002
Summary
Hypoxia has been identified as an important stimulus for gene
expression during embryogenesis and in various pathological
situations. Its influence under physiological conditions,
however, has only been studied occasionally. We therefore
investigated the effect of intermittent high altitude hypoxia on
the mRNA expression of different cytokines and protooncogenes,
but also of other genes described to be regulated by hypoxia, in
the left ventricle (LV), the right ventricle (RV), atria and the
lung of adult rats after simulation of hypoxia in a barochamber
(5000 m, 4 hours to 10 days). Heme oxygenase-1 as well as
transforming growth factor-β1 showed an increased expression in
all regions of the heart and the lung at different periods of
hypoxia. For lactate dehydrogenase-A, we found a significant
up-regulation in the RV and the lung, for lactate dehydrogenase-B
up-regulation in the RV, but down-regulation in the LV and the
atria. Vascular endothelial growth factor was up-regulated in
the RV, the LV and the lung, but down-regulated in the atria.
Its receptor Flk-1 mRNA was significantly increased in the atria
and RV only. Expression of c-fos was found in the LV and RV only
after 4 hours of hypoxia. The level of c-jun was significantly
increased in the LV but decreased in the atria. Our data clearly
demonstrate that intermittent hypoxia is a modulator of gene
expression under physiological conditions. It differently
regulates the expression of distinct genes not only in
individual organs but even within one organ, i.e. in the heart.
Key
words
Hypoxia regulated genes • Transforming growth factor-β •
Vascular endothelial growth factor • c-jun • c-fos
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Elisabeth Deindl, Ph.D., Max-Planck-Institute, Department of
Experimental Cardiology, Benekestrasse 2, D-61231 Bad Nauheim,
Germany. FAX: +49 603 2705419. E-mail
e.deindl@kerckhoff.mpg.de
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