Hepatocyte growth factor is upregulated by low-density lipoproteins and inhibits endothelin-1 release
Hepatocyte growth factor is upregulated by low-density lipoproteins and inhibits endothelin-1 release
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DOI：
10.1152/ajpheart.2000.279.6.h2865
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发表时间：
2000-12-01
影响因子：
4.8
通讯作者：
Rozdzinski, E
中科院分区：
文献类型：
--
作者：
Haug, C;Schmid-Kotsas, A;Rozdzinski, E
已知低密度脂蛋白（LDL）会引起内皮损伤并促进动脉粥样硬化病变的发展。本研究表明，LDL 对培养的人冠状动脉内皮细胞 (HCAEC) 中的肝细胞生长因子 (HGF) 合成（最大释放量：对照的 423 +/- 16%）和 HGF 受体 mRNA 表达具有显着的浓度依赖性刺激作用。 HGF 是内皮细胞的有效有丝分裂原，但不影响平滑肌细胞增殖。相比之下，内皮素-1 (ET-1) 作为血管平滑肌细胞的有丝分裂原，似乎在冠状动脉粥样硬化中表达上调。在本研究中，HGF 浓度依赖性地降低 HCAEC 中的基础 ET-1 合成（最小值：对照的 54 +/- 3%）。这种抑制作用似乎是通过 HGF 受体 c-met 的酪氨酸激酶活性介导的，因为它被酪氨酸激酶抑制剂拉文达斯汀 A 拮抗。此外，HGF 还显着减少了 LDL 刺激的 ET-1 释放。 LDL诱导的HCAEC中HGF合成的上调以及HGF对ET-1合成的抑制作用表明HGF在冠状动脉粥样硬化中具有保护作用。
Low-density lipoproteins (LDL) are known to cause endothelial injury and to promote the development of atherosclerotic lesions. This study demonstrates a significant concentration-dependent stimulatory effect of LDL on hepatocyte growth factor (HGF) synthesis (maximum release: 423 +/- 16% of control) and HGF receptor mRNA expression in cultured human coronary artery endothelial cells (HCAEC). HGF is a potent mitogen for endothelial cells but does not affect smooth muscle cell proliferation. In contrast, endothelin-1 (ET-1) acts as a mitogen on vascular smooth muscle cells and seems to be upregulated in coronary atherosclerosis. In this study, the basal ET-1 synthesis in HCAEC was concentration-dependently reduced by HGF (minimum: 54 +/- 3% of control). This inhibitory effect seems to be mediated via the tyrosine kinase activity of the HGF receptor c-met, since it was antagonized by the tyrosine kinase inhibitor lavendustin A. In addition, HGF also significantly reduced the LDL-stimulated ET-1 release. The LDL-induced upregulation of HGF synthesis in HCAEC and the inhibitory effect of HGF on ET-1 synthesis suggest a protective role of HGF in coronary atherosclerosis.