Angiogeniseis and angiotensin II

血管生成和血管紧张素 II

• 批准号: 13670761
• 负责人: IWASAKA Toshiji
• 金额: $ 2.3万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670761/
• 关键词: angiogenesis; stem cells; regenerative medicine; angiotensin; ARB; angiotensin receptor; アンジオテンシンII; AT1受容体; AT2受容体; HB-EGF

Due to the discovery of nonpeptidic ligands the receptors for angiotensin(Ang) II are classified into two subtypes(AT1-R and AT2-R). AT1-R mediates most of the cardiovascular actions of Ang II. AT2-R is expressed at very high levels in the developing fetus. Its expression is very low in the cardiovascular system of the adult. AT1-R signals stimulate HB-EGF release to activate EGF-R followed by the ERK signaling. This AT1R pathway enhances VEGF releases from myocytes or vascular smooth muscle cells and potenciates angiogenic response. In AT1R KO mice, collateral vessel formation was reduced and mobilization of endothelial progenitor cells was blunted. In AT2R KO mice, ATIR-mediated action was enhanced, comparable with anti-ATIR effect of AT2R. AT2-R activates the kinin/nitric oxide/cGMP system in the cardiovascular systems, resulting in AT2-R-mediated cardioprotection, vasodilation and pressure natriuresis. These effects, transmitted by AT2-R, are mainly exerted by stimulation of protein tyrosine or serine/threonine phosphatases in a Gi-protein-dependent manner. Thus, Ang II stimulates angiogenesis in ischemic lesions via AT1-R, suggesting that in acute myocardial infarction Ang II receptor blocker may attenuate collateral blood flow in acute pahase.

由于非肽类配体的发现，血管紧张素Ⅱ受体分为两个亚型(AT1-R和AT2-R)。AT1-R介导血管紧张素Ⅱ的大部分心血管作用。AT2-R在发育中的胎儿中高水平表达。它在成人心血管系统中的表达很低。AT1-R信号刺激HB-EGF释放，激活EGF-R，继而激活ERK信号。这种AT1R途径可促进心肌细胞或血管平滑肌细胞释放血管内皮生长因子，并增强血管生成反应。在AT1R KO小鼠中，侧支血管形成减少，内皮祖细胞动员迟钝。在AT2R KO小鼠中，ATIR介导的作用增强，与AT2R的抗ATIR作用相当。AT2-R激活心血管系统中的激动素/一氧化氮/cGMP系统，导致AT2-R介导的心脏保护、血管扩张和压力性钠尿。这些效应由AT2-R传递，主要通过蛋白酪氨酸或丝氨酸/苏氨酸磷酸酶的刺激而发挥作用，这种作用依赖于Gi蛋白。因此，Ang II通过AT1-R刺激缺血损伤的血管生成，提示在急性心肌梗死中，Ang II受体阻滞剂可能减少急性心肌梗死的侧支循环血流。

项目成果

Kamihata H, Matsubara H, Nishiue N, Fujiyama S, Amano K, Mori Y, Kojima H, Iwasaka T: "Improvement of Collateral Perfusion and Regional Function by Catheter-Based Implantation of Peripheral Blood Mononuclear Cells into Ischemic Hibernating Myocardium"Arte

Kamihata H、Matsubara H、Nishiue N、Fujiyama S、Amano K、Mori Y、Kojima H、Iwasaka T：“通过导管将外周血单核细胞植入缺血冬眠心肌来改善侧支灌注和区域功能”Arte

Amano K, Matsubara H, 他7人: "Enhancement of ischemia-induces angiogenesis by eNOS expression"Hypertension. 41:2. 156-162 (2003)

Amano K、Matsubara H 和其他 7 人：“eNOS 表达增强缺血诱导血管生成”Hypertension，156-162 (2003)。

Amano K, Matsubara H, Iba O, Fujiyama S, Mori Y, Kojima H, Iwasaka T: "Enhancement of Ischemia-Induced Angiogenesis by eNOS overexpression."Hypertension. 41. 156-162 (2003)

Amano K、Matsubara H、Iba O、Fujiyama S、Mori Y、Kojima H、Iwasaka T：“eNOS 过度表达增强缺血诱导的血管生成。”高血压。

Iba O, Matsubara H, Nozawa Y, Fujiyama S, Amano K, Kojima H, Iwasaka T.: "Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs."Circulation. 106. 2019-2025 (2002)

Iba O、Matsubara H、Nozawa Y、Fujiyama S、Amano K、Kojima H、Iwasaka T.：“通过将外周血单核细胞和血小板植入缺血肢体来实现血管生成。”循环。

Fujiyama S, Matsubara H, Mori Y, Iwasaka T.: "Angiotensin AT1 and AT2 Receptors Differentially Regulate Angiopoietin 2 Expression and VEGF Expression and Angiogenesis by Modulating Heparin Binding EGF-Mediated EOF Receptor Transactivation"Circ Res. 88. 22

Fujiyama S、Matsubara H、Mori Y、Iwasaka T.：“血管紧张素 AT1 和 AT2 受体通过调节肝素结合 EGF 介导的 EOF 受体反式激活来差异调节血管生成素 2 表达和 VEGF 表达和血管生成”Circ Res。