| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Institut fur Pathophysiologie, Zentrum fur Innere Medizin, Universitatsklinikum Essen, Essen, Germany
2 Institut fur Physiologische Chemie, Universitatsklinikum Essen, Essen, Germany
* To whom correspondence should be addressed. E-mail: rainer_schulz{at}uni-essen.de.
In hearts with chronic left ventricular (LV) systolic dysfunction secondary to hypertension or myocardial infarction, mitogen activated protein kinase (MAPK) phosphorylation and/or activity are increased. Whether other settings of LV dysfunction, not associated with ischemia/reperfusion, are also characterized by increased MAPK phosphorylation or activity is unknown. After 3 weeks of rapid LV pacing (400 bpm), 8 rabbits displayed clinical signs of heart failure (HF), and echocardiography revealed an increase in LV end-diastolic diameter from 15.6±0.7(SEM) to 18.8±0.7 mm and a reduced shortening fraction from 31±1 to 10±2% (both p<0.05). Morphological alterations in HF included increased number of TUNEL-positive cardiomyocytes, the extent of fibrosis and cross sectional cardiomyocyte area. Total p38 MAPK did not differ between failing and 8 normal hearts. However, p38 MAPK phosphorylation (164488±29323 vs. 43565±14817 AU, p<0.05, densitometry) and the activities of p38 MAPK alpha and beta were increased in failing compared to normal hearts (149441±38381 and 170430±32952 vs. 68815±28984 and 81788±22774 AU, respectively, both p<0.05). In failing as compared to normal hearts, total and phosphorylated jnk46 and jnk54 MAPK were increased, while total and phosphorylated erk MAPK remained unchanged. Conclusion: In pacing-induced HF, p38 and jnk MAPK phosphorylation as well as p38 MAPK activity are increased. Further studies will have to define whether or not chronic specific blockade of MAPK activity can interfere with apoptosis/fibrosis and thereby attenuate the progression of HF.
This article has been cited by other articles:
|
|
 |
|
  Y. Kuramochi, X. Guo, D. B. Sawyer, and C. C. Lim Rapid electrical stimulation induces early activation of kinase signal transduction pathways and apoptosis in adult rat ventricular myocytes Exp Physiol, July 1, 2006; 91(4): 773 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Eiras, P. Fernandez, R. Pineiro, M. J. Iglesias, J. R. Gonzalez-Juanatey, and F. Lago Doxazosin induces activation of GADD153 and cleavage of focal adhesion kinase in cardiomyocytes en route to apoptosis Cardiovasc Res, July 1, 2006; 71(1): 118 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P D Wheeler-Jones Cell signalling in the cardiovascular system: an overview Heart, October 1, 2005; 91(10): 1366 - 1374. [Full Text] [PDF]
|
|
|
|
 |
|
 E. O. McFalls, M. Hou, R. J. Bache, A. Best, D. Marx, J. Sikora, and H. B. Ward Activation of p38 MAPK and increased glucose transport in chronic hibernating swine myocardium Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1328 - H1334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hanna, S. Cardin, T.-K. Leung, and S. Nattel Differences in atrial versus ventricular remodeling in dogs with ventricular tachypacing-induced congestive heart failure Cardiovasc Res, August 1, 2004; 63(2): 236 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Aker, A. K Snabaitis, I. Konietzka, A. van de Sand, K. Bongler, M. Avkiran, G. Heusch, and R. Schulz Inhibition of the Na+/H+ exchanger attenuates the deterioration of ventricular function during pacing-induced heart failure in rabbits Cardiovasc Res, August 1, 2004; 63(2): 273 - 282. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
