Fosinopril and carvedilol reverse hypertrophy and change the levels of protein kinase C epsilon and components of its signaling complex.

Abstract

OBJECTIVE:

To demonstrate the alterations of Protein Kinase C epsilon (PKC epsilon) and components of its signaling complexes after treatment with fosinopril and carvedilol and analyze potential molecular mechanisms of the two drugs for cardiac hypertrophy and heart failure.

METHODS:

Pressure-overload cardiac hypertrophy (POH) was developed in 8-week-old male Sprague Dawley rats by abdominal aortic banding. The rats were divided into three groups at the age of 20 weeks: POH without failure group, reversed POH with drugs group, and POH with failure group on high diet. Western Blot analysis, co-immunoprecipitation and proteomic analysis were performed in ventricular tissues of rat hearts.

RESULTS:

Increased PKC epsilon was found during POH. PKC epsilon decreased during transition from POH to heart failure (HF). However, increased PKC epsilon inclined to recover to normal levels after treatment with both drugs. There were differential proteins in PKC epsilon complexes during the different stages of POH. The two significant PKC epsilon-binding proteins, MAD1 and Lyn A, were only present in PKC epsilon complex during reversing POH with drugs.

CONCLUSION:

Chronic administration of carvedilol and fosinopril could reverse the development of POH and delay the appearance of HF, partly by regulating PKC epsilon level and its signaling complex. MAD1 and Lyn A may be important proteins participating in the reversing process.

• Authors: Hua He, Wen Wang, Huimin Zhang, Liyuan Ma, Haiying Wu, Peihe Wang, Jiuming Gao
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 20 Issue 4 Pg. 259-71 (Aug 2006) ISSN: 0920-3206 [Print] United States
• PMID: 17039281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic alpha-Antagonists
• Adrenergic beta-Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents
• Carbazoles
• Propanolamines
• Carvedilol
• Protein Kinase C-epsilon
• Fosinopril

Topics

• Adrenergic alpha-Antagonists (pharmacology)
• Adrenergic beta-Antagonists (pharmacology)
• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Antihypertensive Agents (pharmacology)
• Carbazoles (pharmacology)
• Cardiomegaly (drug therapy, enzymology, pathology)
• Carvedilol
• Fosinopril (pharmacology)
• Heart Failure (drug therapy, enzymology, pathology)
• Lung (pathology)
• Male
• Myocardium (enzymology, pathology)
• Propanolamines (pharmacology)
• Protein Kinase C-epsilon (metabolism)
• Proteomics
• Rats
• Rats, Sprague-Dawley
• Signal Transduction