Crabos M, Roth M, Hahn A W, Erne P
Department of Research, University Hospital, Basel, Switzerland.
J Clin Invest. 1994 Jun;93(6):2372-8. doi: 10.1172/JCI117243.
Cardiac hypertrophy is largely due to cardiac fibroblast growth and increased synthesis of extracellular matrix. This study has investigated the contribution of the vasoactive hormone, angiotensin II, toward this hypertrophic process. We have demonstrated that cultures of adult rat cardiac fibroblasts express AT1 but not AT2 receptors for angiotensin II. The ability of angiotensin II to stimulate phosphoinositide catabolism and to elevate intracellular calcium concentrations in these cells was blocked by losartan, a specific AT1 receptor antagonist, but not by the AT2 receptor antagonist CGP 42112. Exposure of adult cardiac fibroblasts to angiotensin II resulted in the induction of several growth-related metabolic events including c-fos protooncogene expression and increased synthesis of DNA, RNA, and protein. Angiotensin II was also found to induce collagen type I, alpha 1 chain transcript expression in cardiac fibroblasts as well as the synthesis and secretion of collagen by these cells. The data demonstrate that angiotensin II, via AT1 receptors, can stimulate cardiac fibroblast growth and increase collagen synthesis in cardiac tissue. Thus, angiotensin II may contribute toward the development of cardiac hypertrophy in conditions of hypertension that are associated with elevated concentrations of angiotensin II.
心肌肥大主要归因于心脏成纤维细胞的生长以及细胞外基质合成的增加。本研究调查了血管活性激素血管紧张素II对这一肥大过程的作用。我们已经证明，成年大鼠心脏成纤维细胞培养物表达血管紧张素II的AT1受体而非AT2受体。血管紧张素II刺激这些细胞中磷酸肌醇分解代谢并提高细胞内钙浓度的能力被特异性AT1受体拮抗剂氯沙坦阻断，但未被AT2受体拮抗剂CGP 42112阻断。成年心脏成纤维细胞暴露于血管紧张素II会导致诱导几种与生长相关的代谢事件，包括c-fos原癌基因表达以及DNA、RNA和蛋白质合成增加。还发现血管紧张素II可诱导心脏成纤维细胞中I型胶原α1链转录本表达以及这些细胞的胶原合成和分泌。数据表明，血管紧张素II通过AT1受体可刺激心脏成纤维细胞生长并增加心脏组织中的胶原合成。因此，在与血管紧张素II浓度升高相关的高血压情况下，血管紧张素II可能促成心肌肥大的发展。
