Abstract |
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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Authors | Yutaka Ohsawa, Haruhiro Toko, Masashi Katsura, Kazue Morimoto, Haruki Yamada, Yaeko Ichikawa, Tatsufumi Murakami, Seitaro Ohkuma, Issei Komuro, Yoshihide Sunada |
Journal | Human molecular genetics
(Hum Mol Genet)
Vol. 13
Issue 2
Pg. 151-7
(Jan 15 2004)
ISSN: 0964-6906 [Print] England |
PMID | 14645200
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cav3 protein, mouse
- Caveolin 3
- Caveolins
- NOS1 protein, human
- NOS3 protein, human
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type I
- Nitric Oxide Synthase Type II
- Nitric Oxide Synthase Type III
- Nos1 protein, mouse
- Nos3 protein, mouse
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Topics |
- Animals
- Cardiomyopathy, Hypertrophic
(etiology, genetics, physiopathology)
- Caveolin 3
- Caveolins
(genetics, metabolism)
- Cytoplasm
(metabolism)
- Gene Expression Regulation
- Humans
- Mice
- Mice, Transgenic
- Mutation
- Myocardial Contraction
- Myocardium
(metabolism)
- Nitric Oxide Synthase
(genetics, metabolism)
- Nitric Oxide Synthase Type I
- Nitric Oxide Synthase Type II
- Nitric Oxide Synthase Type III
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