2003年9月
Human chymase expression in a mice induces mild hypertension with left ventricular hypertrophy
HYPERTENSION RESEARCH
- 巻
- 26
- 号
- 9
- 開始ページ
- 759
- 終了ページ
- 768
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- 出版者・発行元
- JAPANESE SOC HYPERTENSION CENT ACADEMIC SOC, PUBL OFFICE
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 (AT(1)) 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 (AT(1) receptor-dependent) with left ventricular hypertrophy (partially AT(1) receptor-dependent), and also chronic inflammatory changes (AT(1) receptor-independent).
- リンク情報
- ID情報
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- ISSN : 0916-9636
- Web of Science ID : WOS:000186358400014