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首页> 外文期刊>Basic Research in Cardiology: Official Journal of the German Association of Cardiovascular Research >Angiotensin AT1 receptor upregulates expression of basic fibroblast growth factor, basic fibroblast growth factor receptor and coreceptor in human coronary smooth muscle cells.
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Angiotensin AT1 receptor upregulates expression of basic fibroblast growth factor, basic fibroblast growth factor receptor and coreceptor in human coronary smooth muscle cells.

机译:血管紧张素AT1受体上调人冠状动脉平滑肌细胞中碱性成纤维细胞生长因子,碱性成纤维细胞生长因子受体和共受体的表达。

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摘要

Autocrine stimulation and paracrine interaction between coronary smooth muscle cells (cSMC) and endothelial cells (EC) act as regulators of the vascular angiogenesis. Basic fibroblast growth factor (bFGF), its receptor FGF-R1, and coreceptor heparansulfate proteoglycan (HSPG) are important components involved in this angiogenic process. We investigated the influence of angiotensin (Ang) II on this trimolecular bFGF complex, the underlying signaling and the proliferative process in human cSMC. Ang II induces an AT1 receptor-dependent expression of bFGF and also upregulates the FGF-R1 and HSPG expression which is suppressed by losartan, the AT1 receptor blocker. AT1 receptor signaling which is characterized by phosphorylation of p42-mitogen-activated protein kinase (MAPK) is involved in Ang II-induced bFGF, FGF-R1 and HSPG upregulation and DNA synthesis in human cSMC. In contrast, inhibition of the AT2 receptor by PD123,319 has no influence on these Ang II-stimulated and via the MAPK cascade-mediated proangiogenic effects. Finally, our data show that the Ang II-induced DNA synthesis in cSMC is mediated via the bFGF expression. In conclusion, our results suggest that the Ang II-induced angiogenic effects in the vessel wall are supported by the AT1 receptor-stimulated and MAPK pathway-mediated upregulation of the autocrine/paracrine trimolecular bFGF complex in cSMC.
机译:冠状动脉平滑肌细胞(cSMC)和内皮细胞(EC)之间的自分泌刺激和旁分泌相互作用充当血管血管生成的调节剂。碱性成纤维细胞生长因子(bFGF),其受体FGF-R1和共受体肝素硫酸盐蛋白聚糖(HSPG)是此血管生成过程的重要组成部分。我们调查了血管紧张素(Ang)II对这种三分子bFGF复合物,人类cSMC中潜在的信号传导和增殖过程的影响。 Ang II诱导bFGF的AT1受体依赖性表达,并上调FGF-R1和HSPG的表达,而AT1受体阻滞剂losartan抑制了该表达。 AT1受体信号转导的特征在于p42促分裂原活化蛋白激酶(MAPK)的磷酸化,参与人cSMC中Ang II诱导的bFGF,FGF-R1和HSPG上调以及DNA合成。相比之下,PD123,319对AT2受体的抑制作用对这些受Ang II刺激并通过MAPK级联介导的促血管生成作用没有影响。最后,我们的数据表明在cSMC中Ang II诱导的DNA合成是通过bFGF表达介导的。总之,我们的结果表明,血管内皮细胞中Ang II诱导的血管生成作用受到cSMC中AT1受体刺激和MAPK途径介导的自分泌/旁分泌三分子bFGF复合体上调的支持。

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