| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands
2 Micro-array core Facility, VU University Medical Center, Amsterdam, The Netherlands
3 Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: ws.simonides{at}vumc.nl.
Myocardial right-ventricular (RV) hypertrophy due to pulmonary hypertension is aimed at normalizing ventricular wall stress. Depending on the degree of pressure overload, RV hypertrophy may progress to a state of impaired contractile function and heart failure, but this can not be discerned during the early stages of ventricular remodeling. We tested whether critical differences in gene-expression profiles exist between ventricles before the ultimate development of either a compensated or decompensated hypertrophic phenotype. Both phenotypes were selectively induced in Wistar rats by a single subcutaneous injection of either a low or a high dose of the pyrrolizidine alkaloid monocrotaline (MCT). Spotted oligonucleotide micro-arrays were used to investigate pressure-dependent cardiac gene-expression profiles at two weeks after the MCT injections, between control rats and rats that would ultimately develop either compensated or decompensated hypertrophy. Clustering of significantly regulated genes revealed specific expression profiles for each group, although the degree of hypertrophy was still similar in both. The ventricles destined to progress to failure showed activation of pro-apoptotic pathways, particularly related to mitochondria, while the group developing compensated hypertrophy showed blocked pro-death effector signalling via p38 MAPK, through upregulation of MKP1. In summary, we show that already at an early time point, pivotal differences in gene expression exist between ventricles that will ultimately develop either a compensated or a decompensated phenotype, depending on the degree of pressure overload. These data reveal genes that may provide markers for the early prediction of clinical outcome as well as potential targets for early intervention.
This article has been cited by other articles:
|
|
 |
|
  C. Meischl, H. P. Buermans, T. Hazes, M. J. Zuidwijk, R. J. P. Musters, C. Boer, A. van Lingen, W. S. Simonides, M. A. Blankenstein, C. Dupuy, et al. H9c2 cardiomyoblasts produce thyroid hormone Am J Physiol Cell Physiol, May 1, 2008; 294(5): C1227 - C1233. [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]
|
|
|
|
 |
|
 R. R. Lamberts, E. Caldenhoven, M. Lansink, G. Witte, R. J. Vaessen, J. A. St Cyr, and G. J. M. Stienen Preservation of diastolic function in monocrotaline-induced right ventricular hypertrophy in rats Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1869 - H1876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Redout, M. J. Wagner, M. J. Zuidwijk, C. Boer, R. J.P. Musters, C. van Hardeveld, W. J. Paulus, and W. S. Simonides Right-ventricular failure is associated with increased mitochondrial complex II activity and production of reactive oxygen species Cardiovasc Res, September 1, 2007; 75(4): 770 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Pak, A. Aldashev, D. Welsh, and A. Peacock The effects of hypoxia on the cells of the pulmonary vasculature Eur. Respir. J., August 1, 2007; 30(2): 364 - 372. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Lamberts, N. Hamdani, T. W. Soekhoe, N. M. Boontje, R. Zaremba, L. A. Walker, P. P. de Tombe, J. van der Velden, and G. J. M. Stienen Frequency-dependent myofilament Ca2+ desensitization in failing rat myocardium J. Physiol., July 15, 2007; 582(2): 695 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-A. S. Duhaney, L. Cui, M. K. Rude, N. K. Lebrasseur, S. Ngoy, D. S. De Silva, D. A. Siwik, R. Liao, and F. Sam Peroxisome Proliferator-Activated Receptor {alpha}-Independent Actions of Fenofibrate Exacerbates Left Ventricular Dilation and Fibrosis in Chronic Pressure Overload Hypertension, May 1, 2007; 49(5): 1084 - 1094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ashrafian and H. Watkins Reviews of Translational Medicine and Genomics in Cardiovascular Disease: New Disease Taxonomy and Therapeutic Implications: Cardiomyopathies: Therapeutics Based on Molecular Phenotype J. Am. Coll. Cardiol., March 27, 2007; 49(12): 1251 - 1264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Bull, C. D. Coldren, M. W. Geraci, and N. F. Voelkel Gene Expression Profiling in Pulmonary Hypertension Proceedings of the ATS, January 1, 2007; 4(1): 117 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B J M Braakhuis, A Senft, R de Bree, J de Vries, B Ylstra, J Cloos, D J Kuik, C R Leemans, and R H Brakenhoff Expression profiling and prediction of distant metastases in head and neck squamous cell carcinoma J. Clin. Pathol., December 1, 2006; 59(12): 1254 - 1260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. M. Hessel, P. Steendijk, B. den Adel, C. I. Schutte, and A. van der Laarse Characterization of right ventricular function after monocrotaline-induced pulmonary hypertension in the intact rat Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2424 - H2430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Cloos, W. P.H. de Boer, M. H.J. Snel, P. van den IJssel, B. Ylstra, C. R. Leemans, R. H. Brakenhoff, and B. J.M. Braakhuis Microarray Analysis of Bleomycin-Exposed Lymphoblastoid Cells for Identifying Cancer Susceptibility Genes Mol. Cancer Res., February 1, 2006; 4(2): 71 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Liang and B. Ventura Physiological genomics in PG and beyond: July to September 2005 Physiol Genomics, October 17, 2005; 23(2): 119 - 124. [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Bergman, P. P. Eijk, V. W.T. Ruiz van Haperen, K. Smid, G. Veerman, I. Hubeek, P. van den IJssel, B. Ylstra, and G. J. Peters In vivo Induction of Resistance to Gemcitabine Results in Increased Expression of Ribonucleotide Reductase Subunit M1 as the Major Determinant Cancer Res., October 15, 2005; 65(20): 9510 - 9516. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
