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

摘要: A number of in vitro studies have suggested potential pathophysiological roles human (h-) chymase. However, the lack an appropriate animal model has left vivo chymase unclear. To approach this problem, a transgenic mouse (TGM) carrying h-chymase gene was established. The cDNA transgene constructed with chicken βactin promoter and cytomegalovirus immediate early enhancer, injected into oocytes. Homozygous mice high copy suffered from intrauterine death. In three heterozygous TGM lines, expression detected entire organs, including heart, vessels, skin, liver, lung, brain. immunoreactivity localized extracellular matrices each organ, especially on basement membranes vessels. Aortic hepatic chymase-dependent angiotensin II formations were significantly higher than those wild-type littermates. Three independent lines showed same phenotypic changes: elevation blood pressure, ventricular hypertrophy, emaciation reduction lipid tissue, leukocytosis, oligotrichia. subtype 1 (AT1) receptor antagonist valsartan suppressed elevated pressure completely hypertrophy incompletely, but did not affect other phenotypes. These data that caused mild hypertension (AT1 receptor-dependent) (partially AT1 receptor-dependent), also chronic inflammatory changes receptor-independent). (Hypertens Res 2003; 26: 759-768)