INTEGRIN-MEDIATED COLLAGEN GEL CONTRACTION BY CARDIAC FIBROBLASTS - EFFECTS OF ANGIOTENSIN-II
INTEGRIN-MEDIATED COLLAGEN GEL CONTRACTION BY CARDIAC FIBROBLASTS - EFFECTS OF ANGIOTENSIN-II
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DOI：
10.1161/01.res.74.2.291
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发表时间：
1994-02-01
影响因子：
20.1
通讯作者：
BORG, TK
中科院分区：
文献类型：
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作者：
BURGESS, ML;CARVER, WE;BORG, TK
血管紧张素II（Angiotensin II，Ang II）是一种具有血管活性的八肽，与心脏生长、心肌肥厚和继发于高血压的纤维化有关。Ang II的这些结果意味着对心脏间质细胞（成纤维细胞）的功能和形态的影响。本研究旨在（1）确定新生儿心脏成纤维细胞（NHF）的质膜上是否具有功能性Ang II受体，以及（2）使用三维和二维（分别为3D和2D）培养物在体外检查Ang II对NHF的影响。一些分析技术被用来测试本研究的具体问题。由于心脏成纤维细胞表型可能受到培养条件的影响，因此在本研究中使用了2D和3D培养物。逆转录聚合酶链反应和放射性配体结合分析用于测试NHF上Ang II受体的存在。结果表明，2D培养的NHF具有Ang Ⅱ受体mRNA和Ang Ⅱ受体。当分离的NHFs在3D胶原凝胶中培养并用Ang II处理时，NHFs刺激凝胶收缩。这种作用可被特异性Ang II受体拮抗剂[Sar（1）、Ala（8）]Ang II减弱。细胞外基质受体（β 1-整合素）抗体完全抑制Ang II刺激的凝胶收缩（P
Angiotensin II (Ang II), a vasoactive octapeptide, has been implicated in cardiac growth and the development of hypertrophy and fibrosis secondary in hypertensive disease. These consequences of Ang II imply an effect on the function and morphology of cardiac interstitial cells (fibroblasts). The present investigation was designed to (1) determine whether neonatal heart fibroblasts (NHFs) possess functional Ang II receptors on their plasma membrane and (2) examine the effects of Ang II on NHFs in vitro using three- and two-dimensional (3D and 2D, respectively) cultures. Several analytic techniques were used to test the specific questions of the present study. Since cardiac fibroblast phenotype can be influenced by culture conditions, both 2D and 3D cultures were used in the present investigations. Reverse-transcriptase polymerase chain reaction and radioligand binding analysis were used to test for the presence of Ang II receptors on NHFs. Both revealed that NHFs in 2D culture possess Ang II receptor mRNA and Ang II receptors. When isolated NHFs were cultured in 3D collagen gels and treated with Ang II, gel contraction was stimulated by NHFs. This effect was attenuated by the specific Ang II receptor antagonist [Sar(1),Ala(8)]Ang II. Ang II-stimulated gel contraction was completely inhibited by extracellular matrix receptor (beta(1)-integrin) antibodies (P