Acclimatization to chronic hypobaric hypoxia is associated with a differential transcriptional profile between the right and left ventricle

Acute hypobaric hypoxia induces a transient reactivation of the fetal-metabolic gene program in the rat heart. Although chronic hypobaric hypoxia causes alterations in metabolism and cardiac function, little is known about the transcriptional profile associated with acclimatization to chronic hypoxia. Because in chronic hypoxia only the right ventricle is exposed to pressure overload (pulmonary hypertension), we hypothesized that chronic hypobaric hypoxia induces a differential transcriptional profile in the right and left ventricle. Male Wistar rats were exposed to a hypobaric environment (11% O-2) for 4, 10, and 12 weeks. Right and left ventricular tissue was isolated for histology and candidate gene expression. Chronic hypobaric hypoxia induced right ventricular hypertrophy without fibrosis. In the right ventricle, changes in metabolic gene expression suggested a downregulation of fatty acid metabolism and an increase in glucose metabolism, while left ventricular metabolic gene expression suggested restoration of fatty acid metabolism. While myosin heavy chain isoform transcript levels in the right ventricle indicated a progressive reactivation of the fetal iso-gene pattern, there was normalization of myosin iso-gene expression in the left ventricle. Similarly, sarcoendoplasmic reticulum ATPase 2a (SERCA2a) transcript levels in the right ventricle decreased by 12 weeks of chronic hypoxia exposure, whereas, left ventricular SERCA2a expression was unchanged. In conclusion, acclimatization to chronic hypobaric hypoxia induced a differential transcriptional response between the right and left ventricle. We speculate that reactivation of the fetal-metabolic program in the right ventricle is adaptive to pressure overload.