Molecular characterization of angiotensin II--induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype.

作者: J Sadoshima , S Izumo

DOI: 10.1161/01.RES.73.3.413

关键词:

摘要: Increasing evidence suggests that angiotensin II (Ang II) may act as a growth factor for the heart. However, direct effects of Ang on mammalian cardiac cells (myocytes and nonmyocytes), independent secondary hemodynamic neurohumoral effects, have not been well characterized. Therefore, we analyzed molecular phenotype cultured from neonatal rats in response to II. In addition, examined selective receptor subtype antagonists mediating biological myocyte culture, caused an increase protein synthesis without changing rate DNA synthesis. contrast, induced increases synthesis, cell number nonmyocyte cultures (mostly fibroblasts). The II-induced hypertrophic myocytes mitogenic fibroblasts were mediated primarily by AT1 receptor. rapid induction many immediate-early genes (c-fos, c-jun, jun B, Egr-1, c-myc) cultures. "late" markers hypertrophy, skeletal alpha-actin atrial natriuretic expression, within 6 hours myocytes. also upregulation angiotensinogen gene transforming factor-beta 1 hours. Induction genes, late was fully blocked antagonist but AT2 antagonist. These results indicate that: (1) causes hypertrophy mitogenesis fibroblasts, (2) phenotypic changes vitro closely mimic those load-induced vivo, (3) all here are subtype, (4) initiate positive-feedback regulation inducing gene.

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