The role of angiotensin II, endothelin-1 and transforming growth factor-β as autocrine/paracrine mediators of stretch-induced cardiomyocyte hypertrophy
The role of angiotensin II, endothelin-1 and transforming growth factor-β as autocrine/paracrine mediators of stretch-induced cardiomyocyte hypertrophy
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DOI：
10.1023/a:1007279700705
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发表时间：
2001-02-01
影响因子：
4.3
通讯作者：
van der Laarse, A
中科院分区：
文献类型：
--
作者：
van Wamel, AJET;Ruwhof, C;van der Laarse, A
心肌肥厚是心肌组织在机械负荷增加时的代偿反应。在力学因素中，拉伸之后迅速发生肥厚反应。我们试图阐明血管紧张素II （AII）、内皮素-1 （ET-1）和转化生长因子β (tgf - β)在拉伸诱导的心肌细胞肥大中作为自分泌/旁分泌介质的作用。我们从拉伸的心肌细胞和其他拉伸的心肌细胞（如心肌成纤维细胞、内皮细胞和血管平滑肌细胞）中收集条件培养基（CM）。这些CMs被施用于有或没有AII 1型（AT(1)）受体拮抗剂（氯沙坦）、ET-1型A （ETA）受体拮抗剂（BQ610）或抗tgf - β抗体的静止心肌细胞。通过检测原癌基因c-fos和肥大标记基因心房钠肽（ANP）的mRNA水平，表征cm处理的静止心肌细胞的分子表型。我们的研究结果表明，静止心肌细胞中c-fos和ANP的表达在拉伸60min的心肌细胞释放AII后增加。拉伸心肌细胞、心肌成纤维细胞和内皮细胞释放ET-1，导致静止心肌细胞中c-fos和ANP表达增加。被拉伸的VSMCs释放的ET-1和被拉伸的心脏成纤维细胞和内皮细胞释放的tgf - β似乎是静止心肌细胞中ANP表达的旁分泌介质。这些结果表明，AII、ET-1和tgf - β（由心脏和血管细胞类型释放）是拉伸诱导心肌细胞肥大的自分泌/旁分泌介质。因此，在拉伸的心肌中，心肌细胞、心肌成纤维细胞、内皮细胞和VSMCs可能参与细胞间相互作用，导致心肌细胞肥大。
Cardiac hypertrophy is a compensatory response of myocardial tissue upon increased mechanical load. Of the mechanical factors, stretch is rapidly followed by hypertrophic responses. We tried to elucidate the role of angiotensin II (AII), endothelin-1 (ET-1) and transforming growth factor-beta (TGF-beta) as autocrine/paracrine mediators of stretch-induced cardiomyocyte hypertrophy. We collected conditioned medium (CM) from stretched cardiomyocytes and from other stretched cardiac cells, such as cardiac fibroblasts, endothelial cells and vascular smooth muscle cells (VSMCs). These CMs were administered to stationary cardiomyocytes with or without an AII type 1 (AT(1)) receptor antagonist (losartan), an ET-1 type A (ETA) receptor antagonist (BQ610), or anti-TGF-beta antibodies. By measuring the mRNA levels of the proto-oncogene c-fos and the hypertrophy marker gene atrial natriuretic peptide (ANP), the molecular phenotype of the CM-treated stationary cardiomyocytes was characterized.Our results showed that c-fos and ANP expression in stationary cardiomyocytes was increased by AII release from cardiomyocytes that had been stretched for 60 min. Stretched cardiomyocytes, cardiac fibroblasts and endothelial cells released ET-1 which led to increased c-fos and ANP expression in stationary cardiomyocytes. ET-1 released by stretched VSMCs, and TGF-beta released by stretched cardiac fibroblasts and endothelial cells, appeared to be paracrine mediators of ANP expression in stationary cardiomyocytes.These results indicate that AII, ET-1 and TGF-beta (released by cardiac and vascular cell types) act as autocrine/paracrine mediators of stretch-induced cardiomyocyte hypertrophy. Therefore, it is likely that in stretched myocardium the cardiomyocytes, cardiac fibroblasts, endothelial cells and VSMCs take part in intercellular interactions contributing to cardiomyocyte hypertrophy.