Morishita R, Nakamura S, Hayashi S, Aoki M, Matsushita H, Tomita N, Yamamoto K, Moriguchi A, Higaki J, Ogihara T
Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
J Atheroscler Thromb. 1998;4(3):128-34. doi: 10.5551/jat1994.4.128.
HGF is a mesenchyme-derived pleiotropic factor which regulates cell growth, cell motility, and morphogenesis of various types of cells, and is thus considered a humoral mediator of epithelial-mesenchymal interactions responsible for morphogenic tissue interactions during embryonic development and organogenesis. Although HGF is originally identified as a most potent mitogen for hepatocytes, HGF is also belonged to a member of endothelium-specific growth factors. Since endothelial cells are known to secrete various anti-proliferative and vasodilating factors, an agent that promotes seeding or regeneration of endothelium may have potential therapeutic value against vascular smooth muscle cell proliferation. The mitogenic action of HGF on human endothelial cells was most potent among growth factors. Moreover, the presence of local HGF system (HGF and its specific receptor, c-met) was observed in vascular cells and cardiac myocytes in vitro as well as in vivo. Production of local HGF production in vascular cells was regulated by various cytokines including transforming growth factor (TGF)-beta and Ang II. Furthermore, HGF may be therapeutic growth factors for the treatment of restenosis after angioplasty and arteriosclerosis oblerance, etc., as gene therapy. On the other hand, serum HGF concentration was significantly correlated with blood pressure. These results suggest that HGF secretion might be elevated in response to high blood pressure as a counter-system against endothelial dysfunction, and may be considered as an index of severity of hypertension. In this review, we discussed the potential role of HGF in cardiovascular disease.
肝细胞生长因子（HGF）是一种间充质来源的多效性因子，可调节各类细胞的生长、运动及形态发生，因此被认为是上皮-间充质相互作用的体液介质，在胚胎发育和器官形成过程中负责形态发生组织间的相互作用。尽管HGF最初被鉴定为对肝细胞最有效的促有丝分裂原，但它也属于内皮细胞特异性生长因子成员。由于已知内皮细胞可分泌多种抗增殖和血管舒张因子，一种促进内皮细胞种植或再生的药物可能对血管平滑肌细胞增殖具有潜在治疗价值。HGF对人内皮细胞的促有丝分裂作用在生长因子中最为显著。此外，在体外及体内的血管细胞和心肌细胞中均观察到局部HGF系统（HGF及其特异性受体c-met）的存在。血管细胞中局部HGF的产生受包括转化生长因子（TGF）-β和血管紧张素II在内的多种细胞因子调节。此外，作为基因治疗手段，HGF可能是治疗血管成形术后再狭窄和动脉硬化等疾病的治疗性生长因子。另一方面，血清HGF浓度与血压显著相关。这些结果表明，作为对抗内皮功能障碍的一种代偿机制，HGF分泌可能会因高血压而升高，并且可被视为高血压严重程度的一个指标。在本综述中，我们讨论了HGF在心血管疾病中的潜在作用。
