Expression of vascular endothelial growth factor and its receptors correlates closely with formation of the plexiform lesion in human pulmonary hypertension
Expression of vascular endothelial growth factor and its receptors correlates closely with formation of the plexiform lesion in human pulmonary hypertension
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DOI：
10.1046/j.1440-1827.2000.01068.x
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发表时间：
2000-06-01
影响因子：
2.2
通讯作者：
Ikeda, E
中科院分区：
文献类型：
--
作者：
Hirose, S;Hosoda, Y;Ikeda, E
肺动脉高压(PH)患者的肺血管表现出不同的形态变化。其中，丛状病变是最具特征性的血管病变之一，尽管其形成的分子机制尚不清楚。本研究检测了血管内皮细胞特异性血管生成有丝分裂原血管内皮生长因子(VEGF)及其受体FMS样酪氨酸激酶(Flt-1)和含激酶插入结构域受体(KDR)在5例PH患者肺组织中的表达。原位杂交结果显示，血管内皮生长因子在丛状病变内的改良型平滑肌细胞和邻近动脉的中膜平滑肌细胞中均有表达。Flt-1mRNA在邻近丛状病变的动脉内皮细胞有表达，KDR在丛状病变内的血管内皮细胞有表达。血管内皮生长因子免疫定位于表达其受体的内皮细胞和产生血管内皮生长因子的修饰的血管平滑肌细胞。这些结果表明，血管内皮生长因子及其受体表达上调与丛状病变密切相关，提示血管内皮细胞表达的血管内皮细胞可能激活血管内皮细胞形成丛状病变。
The pulmonary vasculature exhibits various morphological changes in patients with pulmonary hypertension (PH). Among them, the plexiform lesion is one of the most characteristic vascular lesions, although nothing is known about the molecular mechanisms of its formation. In the present study, the expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific angiogenic mitogen, and its receptors, fms-like tyrosine kinase (Flt-1) and kinase insert domain-containing receptor (KDR), in the lungs of five cases with PH, were examined. By in situ hybridization, VEGF expression was found in modified smooth muscle cells inside the plexiform lesions as well as in medial smooth muscle cells of the arteries adjacent to the lesions. The expression of Flt-1 mRNA was observed in endothelial cells of the arteries adjacent to the plexiform lesions, while KDR mRNA was expressed in the endothelial cells inside the plexiform lesions. VEGF was immunolocalized to the endothelial cells expressing its receptors as well as the modified smooth muscle cells producing VEGF. These results demonstrate that VEGF and its receptors are upregulated with a close correlation to the plexiform lesions, and suggest that VEGF expressed by smooth muscle cells may activate the endothelial cells to form the plexiform lesions.