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Inhibition of p38 mitogen-activated protein kinase protects the heart against cardiac remodeling in mice with heart failure resulting from myocardial infarction
- Source :
- Journal of cardiac failure. 11(1)
- Publication Year :
- 2005
-
Abstract
- Background Mitogen-activated protein kinases (MAPKs) have emerged as an important pathophysiologic regulator during the development of heart failure (HF). p38 MAPK activity is elevated in cardiac hypertrophy and HF. We used a mouse model of myocardial infarction (MI) to test the hypotheses that (1) inhibition of p38 MAPK activity may improve cardiac function and remodeling after myocardial infarction (MI) and (2) coadministration of a p38 inhibitor (p38i) and an angiotensin-converting enzyme inhibitor (ACEI) may provide only limited further cardioprotection in this model. Methods and results MI was induced in C57BL/6J mice by ligating the left anterior descending coronary artery and then either left untreated or treated with a p38i (SC-409, 30 mg/kg/day in chow), ACEI (enalapril, 20 mg/kg in drinking water), or p38i plus ACEI for 12 weeks. Echocardiography was performed and systolic blood pressure measured before MI and weekly thereafter. At the end of the study, interstitial collagen fraction (ICF) and myocyte cross-sectional area (MCSA) were examined histologically. We found that p38i significantly increased left ventricular ejection fraction and cardiac output and decreased left ventricular area at diastole, ICF, and MCSA. ACEi and p38i each had similar beneficial effects in this mouse model of HF produced by a large MI. Coadministration of p38i and ACEi did not provide any additional benefit. Conclusion Our data suggest that inhibition of p38 MAPK provides significant cardioprotection in mice with HF post-MI.
- Subjects :
- Cardiac function curve
Male
medicine.medical_specialty
Cardiac output
Heart Ventricles
Diastole
Myocardial Infarction
Angiotensin-Converting Enzyme Inhibitors
p38 Mitogen-Activated Protein Kinases
Ventricular Function, Left
Mice
Heart Rate
Internal medicine
medicine
Animals
cardiovascular diseases
Myocardial infarction
Enalapril
Cardiac Output
Cardioprotection
Heart Failure
Ejection fraction
Ventricular Remodeling
business.industry
medicine.disease
Mice, Inbred C57BL
Disease Models, Animal
Endocrinology
Heart failure
Cardiology
Cardiology and Cardiovascular Medicine
business
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 10719164
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of cardiac failure
- Accession number :
- edsair.doi.dedup.....02cde9082c97a886e25019a023b8ab42