Molecular mechanism of role of integrin in hypertensive heart and heart failure

整合素在高血压性心脏病和心力衰竭中作用的分子机制

• 批准号: 13670725
• 负责人: KAWANO Hiroaki
• 金额: $ 1.66万
• 依托单位: Nagasaki 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-13670725/
• 关键词: integrin; cardiac remodeling; hypertension; fibroblast; extracellular matrix; cardiac function; 心エコー

Integrins are a family of transmembrane receptors which were mainly studied on angiogenesis and metastasis of malignant tumor. The interaction of integrins with extracellular matrix protein promotes cell adhesion, spreading, cell migration, and cell proliferation, and they seem to be related to cardiovascular disease. Recently, the beta 1 integrin has been implicated in cardiac hypertrophy. We have researched about the effect of interstitium on cardiac function, especially cardiac fibroblast and integrin system. Integrin system is complicated because more than twenty types of integrins and many types of extracellular matrix proteins. We have already reported that angiotensin II enhances αV, β3, and β5 integrin expressions in cardiac fibroblast and adhesion of cardiac fibroblast to extracellular matrix proteins. Moreover, αV, β3, and β5 integrins of vascular smooth muscle cells, and they are related to vascular smooth muscle cell migration which is related to atherosclerosis.In 2K1C hypertensive heart, these integrins were increased, focal adhesion kinase was activated, and they were accompanied with cardiac remodeling and diastolic dysfunction.

整合素是一个跨膜受体家族，主要研究与恶性肿瘤的血管生成和转移的关系。整合素与细胞外基质蛋白相互作用促进细胞粘附、铺展、迁移和增殖，与心血管疾病有关。最近，β 1整联蛋白已被牵连在心脏肥大。本课题研究了丹参对心脏功能的影响，特别是对心脏成纤维细胞和整合素系统的影响。整合素系统是一个复杂的系统，有二十多种整合素和多种细胞外基质蛋白。我们已经报道了血管紧张素II增强心脏成纤维细胞αV、β3和β5整合素的表达以及心脏成纤维细胞与细胞外基质蛋白的粘附。此外，血管平滑肌细胞的αV、β3、β5整合素与血管平滑肌细胞迁移有关，而血管平滑肌细胞迁移与动脉粥样硬化有关，在2K1C高血压心脏中，这些整合素增加，黏着斑激酶被激活，并伴随心脏重构和舒张功能障碍。

项目成果

Kawano H: "Administration of nifedipineCR immediately after awakening prevents a morning surge in hypertensive patients"Blood Pressure. (in press). (2003)

Kawano H：“醒来后立即服用硝苯地平 CR 可防止高血压患者早晨血压激增”。

Akiyama-Uchida Y: "Norepinephrine enhances fibrosis mediated by TGF-beta in cardiac fibroblasts"Hypertension. 40・2. 148-154 (2002)

Akiyama-Uchida Y：“去甲肾上腺素增强心脏成纤维细胞中 TGF-β 介导的纤维化”高血压 40・2。

Kawano H: "Histological study on the distribution of autonomic nerve in the human heart"Heart and Vessel. (in press). (2003)

Kawano H：“人体心脏自主神经分布的组织学研究”心脏和血管。

Kawano H: "Administration of nifedipine CR immediately after awakening prevents a morning surge hypertensive patients"Blood Pressure. (in press). (2003)

Kawano H：“醒来后立即服用硝苯地平 CR 可防止高血压患者早晨血压激增”。

Imanishi R: "A histone deacetylase inhibitor enhances killing of undifferentiated thyroid carcinoma cells by p53 gene therapy"J Clin Endocrinol Metab. 87・10. 4821-4824 (2002)

Imanishi R：“组蛋白脱乙酰酶抑制剂通过 p53 基因疗法增强对未分化甲状腺癌细胞的杀伤”J Clin Endocrinol Metab 87・10（2002）。