Molecular changes in the early phase of renin-dependent cardiac hypertrophy in hypertensive cyp1a1ren-2 transgenic rats.
An early response to high arterial pressure is the development of cardiac hypertrophy. Functional and transcriptional regulation of ion channels and Ca(2+) handling proteins are involved in this process but the relative contribution of each is unclear. In this study, we investigated the expression of genes involved in action potential generation and Ca(2+) homeostasis of cardiomyocytes in hypertensive cyp1a1ren-2 transgenic rats. In this model, the transgene prorenin was induced by indole-3-carbinol for 2 weeks allowing the induction of hypertension. Electrophysiological recordings from cardiomyocytes of hypertensive rats revealed a slight increase in membrane capacitance consistent with cellular hypertrophy. L-type calcium current density was reduced by 30%. Left ventricles of hypertensive rats showed a significant increase in transcript and protein levels of the cation channel TRPC6 and FK506-binding protein, whereas levels of SERCA2 and voltage-dependent potassium channels K(v)4.2 and K(v)4.3 were found to be decreased. Further, a marked nuclear localization of the transcription factors GATA4 and NFATC4 was observed in cardiac tissue of hypertensive rats. The cyp1a1ren-2 transgenic rat thus appears to be a valid model to investigate early changes in cardiac hypertrophy. This study points to roles for TRPC6, FK506BP, SERCA2, K(v)4.2, and K(v)4.3 in the development of cardiac hypertrophy.
Institute of Pathophysiology, University Medicine Greifswald, Germany.
Christiane
C
Kunert-Keil
Martin
M
Landsberger
Franziska
F
Jantzen
Felix
F
Niessner
Heyo K
HK
Kroemer
Stephan B
SB
Felix
Heinrich
H
Brinkmeier
Jörg
J
Peters
D000200:Action Potentials / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D006332:Cardiomegaly / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis / Q000235:genetics; D006973:Hypertension / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D050778:NFATC Transcription Factors / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D012083:Renin / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism
C506948:Atp2a2 protein, rat; D015220:Calcium Channels; D050991:GATA4 Transcription Factor; D050778:NFATC Transcription Factors; D012333:RNA, Messenger; C535029:Ren2 protein, rat; D050051:Transient Receptor Potential Channels; D019363:Cytochrome P-450 CYP1A1; D012083:Renin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium