Basic Research for Complex Molecular Mechanisms of the Process of the Functional Angiogenesis : toward the development of technologies controlling the molecular target of pathological angiogenesis.

功能性血管生成过程的复杂分子机制的基础研究：开发控制病理性血管生成分子靶标的技术。

基本信息

批准号：
16390118
负责人：
YONEMITSU Yoshikazu
金额：
$ 9.54万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Aim-To make it clear that molecular and cellular mechanisms of physiological and pathophysiological process of angiogenesis, we focused molecular networks among vascular cells (endothelial cells, mural cells, and mesenchymal cells) in view of FGF-2-mediated angiogenic process.Results-1.Using tissue samples of human coronary arteries, we revealed that frequency of an angiogenic/lymphangiogenic factor, VEGF-C corresponded to the AHA grade of athrosclerosis ; however, lymphangiogenesis was a rare event, indicating that VEGF-C functioned as an angiogenic factor rather than a lymphangiogenic factor (published in Human Pathology 2005).2.Using tissue samples of human coronary arteries, we demonstrated that deposition of an antiangiogenic factor, PEDF, was seen as patchy distribution, and negatively correlated to the frequency of intimal angiogenesis (published in Arterioscler Thromb Vasc Biol 2005).3.We showed that PDGF-AA/PDGFRa system, which was previously demonstrated as a controller of VEGF expression in mesenchymal cells (published in Circulation Research 2004), was an essential regulator of VEGF in non-small cell lung cancer as an angiogenic switch (published in Cancer Research 2005).4.The primary abnormality of diabetic microangiopathy was shown as a disease of disturbance of PDGF-BB/PKC axis but not of impaired expression of angiogenic factors (published in Circulation Research 2006).5.We demonstrated that FGF-2 stimulated an lymphangiogenic factor VEGF-C inducing not only lymphangiogenesis, but also capillary stabilization via upregulation of PDGF-BB (submitted).6.FGF-2 stimulates the expression of an inflammatory/arteriogenic chemokine, MCP-1,contributing functional angiogenesis (submitted).Conclusion-These findings reveals the molecular mechanisms of functional and pathological angiogenesis in various human diseases, and suggest the possible molecular targets both of angiogenic and antiangiogenic therapies.

目的表明，清楚地表明，血管生成的生理和病理生理过程的分子和细胞机制，我们聚焦于血管细胞（内皮细胞，壁细胞和间质细胞）之间的分子网络，以FGF-2-2-介导的血管生成过程。因素，VEGF-C对应于AHA的AHA级级。然而，淋巴管生成是一个罕见的事件，表明VEGF-C充当血管生成因子，而不是淋巴管生成因子（在人类病理学2005年发表）。2。人类冠状动脉动脉的组织样本，我们证明了pANTIIM pedf sepliim ped inim pedise nim ped inim feque prectim niged consighty（ Arterioscler血栓VASC Biol 2005）.3。我们表明，以前证明，PDGF-AA/PDGFRA系统是间充质细胞中VEGF表达的控制器（在循环研究中发表）是非小细胞肺癌切换中的VEGF的基本调节剂，是疾病中的非小细胞肺癌的基本调节器（出版于2005年）。微型疾病显示为PDGF-BB/PKC轴的干扰疾病，而不是血管生成因子表达受损的疾病（发表在《循环研究》 2006年中。5。我们证明FGF-2刺激了淋巴管因子VEGF-C vegf-c不仅诱导淋巴生成的生成，而且还通过PD稳定性诱导了PD的上升。（提交）.6.FGF-2刺激炎症/动脉生成趋化因子MCP-1的表达，MCP-1，促进功能性血管生成（提交）。结论 - 这些发现揭示了各种人类疾病中功能和病理血管生成的分子机制，并提出了可能的分子靶标和脉络剂的分子。