Overexpression of P104L mutant caveolin-3 in mice develops hypertrophic cardiomyopathy with enhanced contractility in association with increased endothelial nitric oxide synthase activity
The effect of endogenous nitric oxide synthase (NOS) on cardiac contractility and architecture has been a matter of debate. A role for NOS in cardiac hypertrophy has recently been demonstrated by studies which have shown hypertrophic cardiomyopathy (HCM) with altered contractility in constitutive NO...
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Published in | Human molecular genetics Vol. 13; no. 2; pp. 151 - 157 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Oxford University Press
15.01.2004
Oxford Publishing Limited (England) |
Subjects | |
Online Access | Get full text |
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Summary: | The effect of endogenous nitric oxide synthase (NOS) on cardiac contractility and architecture has been a matter of debate. A role for NOS in cardiac hypertrophy has recently been demonstrated by studies which have shown hypertrophic cardiomyopathy (HCM) with altered contractility in constitutive NOS (cNOS) knockout mice. Caveolin-3, a strong inhibitor of all NOS isoforms, is expressed in sarcolemmal caveolae microdomains and binds to cNOS in vivo: endothelial nitric oxide synthase (eNOS) in cardiac myocytes and neuronal nitric oxide synthase (nNOS) in skeletal myocytes. The current study characterized the biochemical and cardiac parameters of P104L mutant caveolin-3 transgenic mice, a model of an autosomal dominant limb-girdle muscular dystrophy (LGMD1C). Transgenic mouse hearts demonstrated HCM, enhanced basal contractility, decreased left ventricular end diastolic diameter, and loss and cytoplasmic mislocalization of caveolin-3 protein. Surprisingly, cardiac muscle showed activation of eNOS catalytic activity without increased expression of all NOS isoforms. These data suggest that a moderate increase in eNOS activity associated with loss of caveolin-3 results in HCM. |
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Bibliography: | To whom correspondence should be addressed: Tel: +81 864621111; Fax: +81 864621199; Email: ysunada@med.kawasaki-m.ac.jp local:ddh014 istex:0C12AAF0B25EFE79AA582E6E0CC7C4B7494B0281 ark:/67375/HXZ-WN1KKPZK-N ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0964-6906 1460-2083 1460-2083 |
DOI: | 10.1093/hmg/ddh014 |