Hypertrophic phenotype of cardiac calcium/ calmodulin-dependent protein kinase II is reversed by angiotensin converting enzyme inhibition

Item Type:	Article
Title:	Hypertrophic phenotype of cardiac calcium/ calmodulin-dependent protein kinase II is reversed by angiotensin converting enzyme inhibition
Creators Name:	Hempel, P. and Hoch, B. and Bartel, S. and Karczewski, P.
Abstract:	Calcium-dependent mechanisms and the renin angiotensin system (RAS) are critically involved in the hypertrophic growth of the myocardium. The calcium/calmodulin-dependent protein kinase II (CaMKII) is a ubiquitous mediator in calcium signaling and modulates calcium handling and growth mechanisms in cardiomyocytes. Here we present data on expression of cardiac isoforms of CaMKII{delta}, the dominant form in the myocardium, in compensatory hypertrophy of stroke-prone spontaneously hypertensive rats (SHRSP) compared to the normotensive Wistar-Kyoto (WKY) control strain. Cardiac hypertrophy in SHRSP was documented by an increased heart weight/body weight ratio (HW/BW) of 31 % (p < 0.05) and a more than six-fold elevated atrial natriuretic factor (ANF) transcript level (p < 0.05). Compensatory hypertrophic growth in SHRSP produced a specific phenotype of CaMKII{delta} isoforms characterized by increased transcript levels of the embryonic/neonatal isoform {delta}4 (48%, p < 0.05) and the isoform {delta}9 (31%, p < 0.05) with no changes in {delta}2 and {delta}3. Inhibition of angiotensin converting enzyme (ACE) by cilazapril completely regressed myocardial hypertrophy, normalized ANF transcript levels, and restored the normal phenotype of CaMKII{delta} by reducing transcripts for {delta}4 and {delta}9 to levels present in WKY controls. Our data suggest the importance of specific changes in the CaMKII isoform composition for growth processes in the myocardium.
Keywords:	Angiotensin Converting Enzyme Inhibition, Calcium/Calmodulin-Dependent Protein Kinase II, Myocardial Hypertrophy, Stroke-Prone Spontaneously Hypertensive Rats, Animals, Rats
Source:	Basic Research in Cardiology
ISSN:	0300-8428
Publisher:	Springer
Volume:	97
Number:	1
Page Range:	I/96-I/101
Date:	May 2002
Official Publication:	https://doi.org/10.1007/s003950200037
PubMed:	View item in PubMed

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