| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Division of Cardiology, Department of Internal Medicine, University of Texas Houston Medical School, Houston, TX, USA
2 Hatter Institute for Cardiology Research, University of Cape Town Faculty of Health Science, Cape Town, South Africa
* To whom correspondence should be addressed. E-mail: Heinrich.Taegtmeyer{at}uth.tmc.edu.
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. While 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 (ANF) 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 (SERCA2a) 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.
This article has been cited by other articles:
|
|
 |
|
  O. Arjamaa and M. Nikinmaa Natriuretic peptides in hormonal regulation of hypoxia responses Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2009; 296(2): R257 - R264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ambalavanan, T. Nicola, J. Hagood, A. Bulger, R. Serra, J. Murphy-Ullrich, S. Oparil, and Y.-F. Chen Transforming growth factor-{beta} signaling mediates hypoxia-induced pulmonary arterial remodeling and inhibition of alveolar development in newborn mouse lung Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L86 - L95. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pokreisz, G. Marsboom, and S. Janssens Pressure overload-induced right ventricular dysfunction and remodelling in experimental pulmonary hypertension: the right heart revisited Eur. Heart J. Suppl., December 1, 2007; 9(suppl_H): H75 - H84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Essop Cardiac metabolic adaptations in response to chronic hypoxia J. Physiol., November 1, 2007; 584(3): 715 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zungu, M. P. Alcolea, F. J. Garcia-Palmer, M. E. Young, and M. F. Essop Genomic modulation of mitochondrial respiratory genes in the hypertrophied heart reflects adaptive changes in mitochondrial and contractile function Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2819 - H2825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Lourenco, R. Roncon-Albuquerque Jr., C. Bras-Silva, B. Faria, J. Wieland, T. Henriques-Coelho, J. Correia-Pinto, and A. F. Leite-Moreira Myocardial dysfunction and neurohumoral activation without remodeling in left ventricle of monocrotaline-induced pulmonary hypertensive rats Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1587 - H1594. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
