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.

点击翻译按钮获取中文摘要

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.