Pathophysiological Mechanisms of Angiogenesis-Related Diseases

血管生成相关疾病的病理生理机制

• 批准号: 18390115
• 负责人: YONEMITSU Yoshikazu
• 金额: $ 10.77万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390115/
• 关键词: Generation and Development of Blood vessels; Generation of Lymphatic vessels; Sendai Virus Vector; MCP-1; FGF-2; PDGF-BB; Spred; PKC eta; 血管新生; 動脈硬化; 間葉系細胞

During 2-years' research project, we performed integrated research approach, from cell, animal model, to human materials, to investigate the genetic, molecular, and pathophysiological mechanisms of angiogenesis-related diseases.Major findings obtained in this project were as follows; 1. We clarified the critical role of monocyte/macrophage chamoattractant protein-1 (MCP 1) during revascularization mediated by FGF-2 (published in Arteriosclr Thromb Vasc Biol 2006). 2. We identified a new single nucleotide polymorphism (SNP) of protein kinase-C (PKC) eta critically related to cerebral infarction (published in Nature Genetics 2006). 3. We discovered the deposition of oxidized lipids at subintimal layer prior to macrophage accumulation in very early process of human atherosclerosis (published in Arteriosclr Thromb Vasc Biol 2006). 4. We established a double knockout mouse line for endogenous growth factor inhibitors, namely Spred-1 and Spred-2. Mice of this line exhibited embryonic lethal at day 13.5, that were caused by abnormal development of lymphatic vessels due to VEGFR3 signaling (Mol Cell Biol 2007). 5. A ligand of VEGRR1, placental growth factor (PlGF), support the function of VEGF-A during FGF-2-mediated angiogenesis (Atherosclerosis 2008). 6. FGF-2 upregulates VEGF-C expression to form functional capillary and lymphatic network associated with PDGF-BB expression (manuscript under submission). 7. Statins restore vascular endothelial function under diabetic state nitric oxide (NO)/ endothelial NO syntase (eNOS), but not capillary maturation by PDGF-BB, is critical in this process.These findings should contribute the understanding of and new therapeutic approach to atherosclerotic diseases and metabolic syndrome.

在两年的研究项目中，我们采取了综合研究方法，从细胞，动物模型到人类材料，研究与血管生成相关疾病的遗传，分子和病理生理机制。在该项目中获得的Major发现如下； 1。我们阐明了由FGF-2介导的血运重建过程中单核细胞/巨噬细胞折叠蛋白1（MCP 1）的关键作用（发表在Arteriosclr血栓Vasc Biol 2006中）。 2。我们确定了一种与脑梗死密切相关的蛋白激酶-C（PKC）ETA的新单核苷酸多态性（SNP）（自然遗传学2006年）。 3。我们在人动脉粥样硬化的早期过程中发现了巨噬细胞积累之前的氧化脂质在下层的层中的沉积（发表在Arteriosclr Thromb Vasc Biol 2006中）。 4。我们建立了一条双基因敲除小鼠系，用于内源性生长因子抑制剂，即SPRSPERSED-1和SPRED-2。该线的小鼠在第13.5天表现出胚胎致死，这是由于VEGFR3信号传导引起的淋巴管异常发育引起的（Mol Cell Biol 2007）。 5。VEGRR1的配体，胎盘生长因子（PLGF），支持FGF-2介导的血管生成过程中VEGF-A的功能（动脉粥样硬化2008）。 6. FGF-2上调VEGF-C表达，形成与PDGF-BB表达相关的功能毛细管和淋巴网络（在提交中的手稿）。 7.他汀类药物在糖尿病状态氧化物（NO）/内皮NO语法酶（ENOS）下恢复血管内皮功能，而不是PDGF-BB的毛细血管成熟，这在此过程中至关重要。这些发现应促进对动脉粥样硬化疾病的理解和新的治疗方法，从而对动脉粥样硬化疾病和新的治疗方法进行理解。

项目成果

『Vascular regenaration〜Dawn of Vascular generative medici ne: Practial use in comingup』 (Ryuichi, Morishita edit) The third chapter Angiogenic Growth Factor i) Fibrobrlast Growth Factor (FGF)

《血管再生〜血管生成医学的黎明：未来的实际应用》（森下龙一编辑）第三章血管生成因子i）成纤维细胞生长因子（FGF）

• 发表时间: 2008
• 期刊: Shinko Trading CO LTD Publication Department 251
• 作者: Misu Y;Goshima Y;Yonemitsu Y
• 通讯作者: Yonemitsu Y

Deletion of All Membranous Genes of Recombinant Sendai Virus Results in the Dramatic Reduction of Toxicity for Pulmonary GeneTransfer in Neonatal Mice.

删除重组仙台病毒的所有膜基因可显着降低新生小鼠肺部基因转移的毒性。

• 发表时间: 2006
• 作者: Tanaka S;et al.
• 通讯作者: et al.

Development and Characterization of Immunotherapy Usi SeV/dF-Activated Dendritic Cells against Squamous Cell Carcinoma

使用 SeV/dF 激活的树突状细胞对抗鳞状细胞癌的免疫疗法的开发和表征

• 发表时间: 2006
• 作者: Yoneyama Y;et al.;Matsunaga A. et al.
• 通讯作者: Matsunaga A. et al.

'Recombinant Sendai Virus as a Novel RNA Drug (DVC1-0101) to Treat Critical Limb Ischemia'

“重组仙台病毒作为新型 RNA 药物 (DVC1-0101) 治疗严重肢体缺血”

• 发表时间: 2007
• 作者: 鬼丸満穂;他;米満吉和;米満吉和;Yonemitsu Y;米満 吉和;米満吉和;Yonemitsu Y;米満 吉和;米満 吉和;米満 吉和;米満 吉和;Yonemitsu Y.;Yonemitsu Y.;Yonemitsu Y.;米満 吉和;米満 吉和;米満吉和
• 通讯作者: 米満吉和

Generation of a large number of dendritic cells in vitro for cancer imm unotherapy

体外产生大量树突状细胞用于癌症免疫治疗

• 发表时间: 2007
• 作者: Harada Y;et al.
• 通讯作者: et al.