| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Departments of Surgery
2 Statistics
3 Medicine, Duke University Medical Center, Durham, North Carolina 27710
Numerous murine models of heart failure (HF) have been described, many of which develop progressive deterioration of cardiac function. We have recently demonstrated that several of these can be "rescued" or prevented by transgenic cardiac expression of a peptide inhibitor of the ß-adrenergic receptor kinase (ßARKct). To uncover genomic changes associated with cardiomyopathy and/or its phenotypic rescue by the ßARKct, oligonucleotide microarray analysis of left ventricular (LV) gene expression was performed in a total of 53 samples, including 12 each of Normal, HF, and Rescue. Multiple statistical analyses demonstrated significant differences between all groups and further demonstrated that ßARKct Rescue returned gene expression toward that of Normal. In our statistical analyses, we found that the HF phenotype is blindly predictable based solely on gene expression profile. To investigate the progression of HF, LV gene expression was determined in young mice with mildly diminished cardiac function and in older mice with severely impaired cardiac function. Interestingly, mild and advanced HF mice shared similar gene expression profiles, and importantly, the mild HF mice were predicted as having a HF phenotype when blindly subjected to our predictive model described above. These data not only validate our predictive model but further demonstrate that, in these mice, the HF gene expression profile appears to already be set in the early stages of HF progression. Thus we have identified methodologies that have the potential to be used for predictive genomic profiling of cardiac phenotype, including cardiovascular disease.
genomics; microarrays
This article has been cited by other articles:
|
|
 |
|
  N. S. Rajasekaran, M. A. Firpo, B. A. Milash, R. B. Weiss, and I. J. Benjamin Global expression profiling identifies a novel biosignature for protein aggregation R120GCryAB cardiomyopathy in mice Physiol Genomics, October 8, 2008; 35(2): 165 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zhu, A. A. Gach, G. Liu, X. Xu, C. C. Lim, J. X. Zhang, L. Mao, K. Chuprun, W. J. Koch, R. Liao, et al. Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active G{alpha}o* protein Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1335 - H1347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Bullard, T. L. Protack, F. Aguilar, S. Bagwe, H. T. Massey, and B. C. Blaxall Identification of Nogo as a novel indicator of heart failure Physiol Genomics, January 17, 2008; 32(2): 182 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pawlinski, M. Tencati, C. R. Hampton, T. Shishido, T. A. Bullard, L. M. Casey, P. Andrade-Gordon, M. Kotzsch, D. Spring, T. Luther, et al. Protease-Activated Receptor-1 Contributes to Cardiac Remodeling and Hypertrophy Circulation, November 13, 2007; 116(20): 2298 - 2306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Dunnick, K. A. Thayer, and G. S. Travlos Inclusion of Biomarkers for Detecting Perturbations in the Heart and Lung and Lipid/Carbohydrate Metabolism in National Toxicology Program Studies Toxicol. Sci., November 1, 2007; 100(1): 29 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mirotsou, V. J. Dzau, R. E. Pratt, and E. O. Weinberg Physiological genomics of cardiac disease: quantitative relationships between gene expression and left ventricular hypertrophy Physiol Genomics, January 12, 2007; 27(1): 86 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rajan, S. S. Williams, G. Jagatheesan, R. P. H. Ahmed, G. Fuller-Bicer, A. Schwartz, B. J. Aronow, and D. F. Wieczorek Microarray analysis of gene expression during early stages of mild and severe cardiac hypertrophy Physiol Genomics, November 21, 2006; 27(3): 309 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Pandya, H.-S. Kim, and O. Smithies Fibrosis, not cell size, delineates beta-myosin heavy chain reexpression during cardiac hypertrophy and normal aging in vivo PNAS, November 7, 2006; 103(45): 16864 - 16869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Schiekofer, I. Shiojima, K. Sato, G. Galasso, Y. Oshima, and K. Walsh Microarray analysis of Akt1 activation in transgenic mouse hearts reveals transcript expression profiles associated with compensatory hypertrophy and failure Physiol Genomics, October 11, 2006; 27(2): 156 - 170. [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]
|
|
|
|
|
|
S. W. Kong, N. Bodyak, P. Yue, Z. Liu, J. Brown, S. Izumo, and P. M. Kang Genetic expression profiles during physiological and pathological cardiac hypertrophy and heart failure in rats Physiol Genomics, March 21, 2005; 21(1): 34 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Schwartz, A. Duka, I. Duka, J. Cui, and H. Gavras Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H1957 - H1966. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
