Dynamic changes of gene expression in hypoxia-induced right ventricular
hypertrophy.
Sharma, Saumya, Heinrich Taegtmeyer, Julia Adrogue, Peter Razeghi, Shiraj Sen,
Kholiswa Ngumbela, and M. Faadiel Essop.
1Division of Cardiology, Department of Internal Medicine, University of Texas-
Houston Medical School, Houston, Texas 77030; and 2Hatter Institute for Cardiology
Research, University of Cape Town Faculty of Health Science, Cape Town, South Africa,
7925
APStracts 10:0416H, 2003.
Hypobaric hypoxia induces right ventricular hypertrophy. The relative contribution of
pulmonary hypertension, decreased arterial oxygen, and neuroendocrine stimulation to
the transcriptional profile of hypoxia-induced right ventricular hypertrophy is unknown.
Whereas both ventricles are exposed to hypoxia and neuroendocrine stimulation, only the
right ventricle is exposed to increased load. We postulated that right ventricular
hypertrophy would reactivate the fetal gene transcriptional profile in response to
increased load. We measured the expression of candidate genes in the right ventricle of
rats exposed to hypobaric hypoxia (11% O2) and compared the results to the left
ventricle. Hypoxia induced right ventricular hypertrophy without fibrosis. In the right
ventricle only, atrial natriuretic factor transcript levels progressively increased starting at
7 days. Metabolic genes were differentially regulated suggesting a substrate switch from
fatty acids to glucose during early hypoxia and a switch back to fatty acids by 14 days.
There was also a switch in myosin isogene expression and a downregulation of
sarcoplasmic/endoplasmic ATPase 2a during early hypoxia, whereas later, both myosin
isoforms and SERCA2a were upregulated. When comparing right and left ventricle, the
transcript levels of all genes, except for myosin isoforms and pyruvate dehydrogenase
kinase-4 (PDK-4), differed dramatically suggesting that all these genes are regulated by
load. Our findings demonstrate that hypoxia-induced right ventricular hypertrophy
transiently reactivates the fetal gene program. Furthermore, myosin iso-gene and PDK-4
expression are not affected by load, suggesting that either hypoxia itself or
neuroendocrine stimulation is the primary regulator of these genes.
Received 25 September 2003; accepted in final form 18 November 2003
APS Manuscript Number H916-3.
Article publication pending Am J Physiol Heart Circ Physiol
ISSN 1080-4757 Copyright 2003 The American Physiological Society.
Published in APStracts on 19 December 2003