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Human chymase expression in a mice induces mild hypertension with left ventricular hypertrophy.

Authors: Koga, T  Urata, H  Inoue, Y  Hoshino, T  Okamoto, T  Matsunaga, A  Suzuki, M  Miyazaki, J  Ideishi, M  Arakawa, K  Saku, K 
Citation: Koga T, etal., Hypertens Res. 2003 Sep;26(9):759-68.
Pubmed: (View Article at PubMed) PMID:14620933

A number of in vitro studies have suggested potential pathophysiological roles of human (h-) chymase. However, the lack of an appropriate animal model has left the in vivo roles of chymase unclear. To approach this problem, a transgenic mouse (TGM) model carrying the h-chymase gene was established. The h-chymase cDNA transgene was constructed with the chicken beta actin promoter and cytomegalovirus immediate early gene enhancer, and injected into mouse oocytes. Homozygous mice with a high copy number of the h-chymase gene suffered from intrauterine death. In three heterozygous TGM lines, h-chymase transgene expression was detected in entire organs, including the heart, vessels, skin, liver, lung, and brain. The h-chymase immunoreactivity was localized in the extracellular matrices of each organ, especially on the basement membranes of vessels. Aortic and hepatic chymase-dependent angiotensin II formations were significantly higher than those in the wild-type littermates. Three independent TGM lines showed the same phenotypic changes: elevation of blood pressure, left ventricular hypertrophy, emaciation with reduction in the lipid tissue, leukocytosis, and oligotrichia. The angiotensin II subtype 1 (AT1) receptor antagonist valsartan suppressed the elevated blood pressure completely and left ventricular hypertrophy incompletely, but did not affect the other phenotypes. These data suggested that in vivo expression of h-chymase caused mild hypertension (AT1 receptor-dependent) with left ventricular hypertrophy (partially AT1 receptor-dependent), and also chronic inflammatory changes (AT1 receptor-independent).

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CRRD Object Information
CRRD ID: 5128600
Created: 2011-03-11
Species: All species
Last Modified: 2011-03-11
Status: ACTIVE



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