Gray M O, Long C S, Kalinyak J E, Li H T, Karliner J S
San Francisco Veterans Affairs Medical Center, Department of Medicine, University of California, San Francisco 94121, USA.
Cardiovasc Res. 1998 Nov;40(2):352-63. doi: 10.1016/s0008-6363(98)00121-7.
We sought to determine whether angiotensin II (Ang II) promotes hypertrophy of cardiac directly or via paracrine mechanisms mediated by cardiac fibroblasts.
We studied neonatal rat cardiac myocytes and fibroblasts in culture as a model system. Paracrine effects of Ang II were identified using conditioned medium and co-culture experiments.
Ang II type 1 (AT1) receptors responsible for myocyte growth localized to fibroblasts in radioligand binding, emulsion autoradiography, Western analysis, and immunofluorescence staining experiments. The bulk of AT1 receptor binding in myocyte cultures (1343 +/- 472 sites/cell) was to Ang II receptors on contaminating fibroblasts (9747 +/- 2126 sites/cell). Ang II induced significant paracrine trophic effects on myocytes in conditioned medium (40% increase in protein synthesis over control) and co-culture (4-fold increase over control) experiments. TGF-beta 1 and endothelin-1 were paracrine mediators of hypertrophy in neutralization experiments.
Ang II stimulates cardiac myocyte hypertrophy via paracrine release of TGF-beta 1 and endothelin-1 from cardiac fibroblasts in a neonatal rat cell culture model.
我们试图确定血管紧张素II（Ang II）是直接促进心肌肥大，还是通过心脏成纤维细胞介导的旁分泌机制来促进。
我们以培养的新生大鼠心肌细胞和成纤维细胞作为模型系统进行研究。使用条件培养基和共培养实验来确定Ang II的旁分泌作用。
在放射性配体结合、乳胶放射自显影、蛋白质印迹分析和免疫荧光染色实验中，负责心肌细胞生长的1型Ang II（AT1）受体定位于成纤维细胞。心肌细胞培养物中大部分的AT1受体结合（1343±472个位点/细胞）是与污染的成纤维细胞上的Ang II受体结合（9747±2126个位点/细胞）。在条件培养基（蛋白质合成比对照增加40%）和共培养（比对照增加4倍）实验中，Ang II对心肌细胞产生了显著的旁分泌营养作用。在中和实验中，转化生长因子-β1（TGF-β1）和内皮素-1是肥大的旁分泌介质。
在新生大鼠细胞培养模型中，Ang II通过心脏成纤维细胞旁分泌释放TGF-β1和内皮素-1来刺激心肌细胞肥大。
