Molecular pathological studies on physiological function of VEGF in atherosclerotic Vessels

VEGF在动脉粥样硬化血管中生理功能的分子病理学研究

• 批准号: 09470064
• 负责人: NAKAGAWA Kazunori
• 金额: $ 8.13万
• 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470064/
• 关键词: Atheroscrelosis; Endothelial Cell; Angiogenesis; Gene Transfer; 血管内皮細胞増殖因子; 血栓形成

The cellular interaction has been considered to play a critical role in pathophysiology of blood vessel. However, its pathophysiologic roles and mechanisms still remain unclear. To clarify the patho-biological implication of cellular interaction in vessel wall, we performed histochemical, cell biological or genetical analyses in vitro and we developed new technique (gene transfer of decoy for transcription factor). Co-culture experiment of endothelial cells and mononuclear cells revealed that thrombogenic activity of endothelial cells was induced though the cross-talk with the IL-l beta and TNF-alpha secreated by mononuclear cells. By histochemical analysis of atherosclerotic intima, the number of VEGF-positive cells (the smooth muscle cells, foamy macrophages) was positively correlated to the number of intimal blood vessels. These findings indicated that the VEGF can act as a local and endogenous regulator of endothelial cell functions. The transfer of decoy for cis-element in promoter region of angiogenic factors would be effective method for regulating the angiogenesis, since some angiogenic factors expression promoted by such cis-element could be simultaneously suppressed. These results and techniques may provide a new insight for more comprehensive on cell function in vessel walls as well as therapeutic implications in vascular diseases.

细胞间的相互作用在血管的病理生理学中起着重要的作用。然而，其病理生理作用和机制仍不清楚。为了阐明血管壁细胞相互作用的病理生物学意义，我们进行了组织化学，细胞生物学或遗传学分析，在体外，我们开发了新的技术（诱饵转录因子的基因转移）。内皮细胞与单核细胞共培养实验表明，内皮细胞的血栓形成活性是通过与单核细胞分泌的IL-1 β和TNF-α相互作用而诱导的。动脉粥样硬化内膜组织化学分析显示，VEGF阳性细胞（平滑肌细胞、泡沫巨噬细胞）数量与内膜血管数量呈正相关。这些发现表明VEGF可以作为内皮细胞功能的局部和内源性调节剂。在血管生成因子的启动子区引入诱饵元件，可以同时抑制由该元件促进的某些血管生成因子的表达，是调控血管生成的有效方法。这些结果和技术可能为更全面地研究血管壁细胞功能以及血管疾病的治疗意义提供新的见解。

项目成果

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