Prevention of Cardiac9 Remodeling and Diastolic Dysfunction by inhibiting Fibrotic Process.

通过抑制纤维化过程预防心脏重塑和舒张功能障碍。

• 批准号: 12670711
• 负责人: KAI Hisashi
• 金额: $ 2.3万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670711/
• 关键词: TGF-β; myocardial fibrosis; hypertension; diastolic dysfunction; pressure-overloaded hearts; HVJリポゾーム; HVJリポソーム; 可溶性TβRIIIgGキメラ遺伝子; HVJリボソーム

Excessive myocardial fibrosis impairs cardiac function in hypertensive hearts. Roles of transforming growth factor (TGF)-B in myocardial remodeling and cardiac dysfunction were examined (in press)ure-overloaded rats.Pressure overload was induced by a suprarenal aortic constriction in Wistar rats. Fibroblast activation (proliferation and phenotype transition to myofibroblasts) was observed after day 3 and peaked at days 3-7. Thereafter, myocyte hypertrophy and myocWdial fibrosis developed by day 28. At day 28, echocardiography showed normal LV fractional shortening but the decreased early to late filling ratio of the transmitral Doppler velocity, and hemodynamic measurement revealed LV end-diastolic pressure elevation, indicating normal systolic but abnormal diastolic function. Myocardial TGF-B mRNA expression was induced after day 3, peaked at day 7, and remained modestly increased at day 28.An anti-TGF-B neutralizing antibody (NAb), which was intraperitoneally administered daily from 1 day before operation, inhibited fibroblast activation and subsequently prevented collagen mRNA induction and myocardial fibrosis, but not myocyte hypertrophy. NAb reversed diastolic dysfunction without affecting blood pressure and systolic function.TGF-B plays a causal role in myocardial fibrosis and diastolic dysfunction through fibroblast activation in

过度的心肌纤维化会损害高血压心脏的心脏功能。检查了转化生长因子（TGF）-b在心肌重塑和心脏功能障碍中的作用（在印刷中）URE量超过的大鼠。按压超负荷是由Wistar大鼠的上主动脉上收缩引起的。第3天后观察到成纤维细胞激活（增殖和表型过渡到肌纤维细胞），并在第3-7天达到峰值。此后，在第28天开始开发的肌细胞肥大和肌纤维纤维化。在第28天，超声心动图显示正常的LV分数缩短，但早期与晚期填充率的降低率降低了跨性别多普勒多普勒的速度，并且血液动力学测量显示出LV终止压力静脉升压率，表明正常的抑制性抑制率高。但是舒张功能异常。第3天后诱导心肌TGF-B mRNA表达，在第7天达到峰激活并随后防止胶原蛋白mRNA诱导和心肌纤维化，但不能阻止心肌细胞肥大。 NAB反转舒张功能障碍而不会影响血压和收缩功能。TGF-B通过成纤维细胞激活在心肌纤维化和舒张功能障碍中起因果作用