Relationship between changes in response to mechanoreceptor stimulation of endocardial endothelial cells and the development of heart failure

心内膜内皮细胞机械感受器刺激反应的变化与心力衰竭发展的关系

• 批准号: 10670043
• 负责人: HASHIMOTO Michio
• 金额: $ 2.05万
• 依托单位: Shimane 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670043/
• 关键词: Endocardial endothelial cells; Mechanoreceptor; Shear stress; Transmural pressure; Prostacycline; Aging; Heart failure; Rats; 心不全; 一酸化窒素; 細胞内Caストアー

We estimated the effects of mechanical stress such as shear stress and transmural pressure on the production of vasoactive substances from endocardial endothelial cells (EECs) isolated from porcine hearts and from young (5-week-old) and aged (100-week-old) rat hearts. We also demonstrated age-related changes in rat cardiac functions, with the Langendorff and Working heart apparatus.Results and Conclusion1 : Shear stress (0.2〜6dyne/cmィイD12ィエD1) and transmural pressure (0〜150mmHg) increased prostacycline (PGIィイD22ィエD2) production from porcine EECs. Shear stress-induced PGIィイD22ィエD2 production was significantly inhibited from cells exposed to 8-(dimetylamino) octyl 3, 4, 5-trimethoxybenzoate hydrochloride (an inhibitor of intracellular calcium mobilization) or cyclopiazonic acid ( and endoplasmic reticulum CaィイD12+ィエD1-ATPase inhibitor) ; moreover, the production decreased from EECs of aged rats rather than from those of young rats.2 : Proliferation of rat EECs decreased with aging, in association with the morphological enlargement of the cells.3 : Phase-contrast electron microscopy revealed the enlargement of right ventricular EECs isolated from rat hearts with right ventricular hypertrophy induced by subcutaneous injection of monocrotaline.4 : Cardiac output, aortic flow and heart rates of rats decreased significantly with advancing age.Shear stress enhances PGIィイD22ィエD2 production from EECs, and the mechanotransduction of shear stress depends on calcium mobilization in EECs. in rats mechanotransduction decreased with aging, and, morphologically, the right ventricular EECs enlarged with advancing age and with right ventricular hypertrophy. These results suggest that endocardial dysfunction participates in the development of heart failure.

我们估计了机械应力（如剪切应力和跨壁压力）对从猪心脏和幼龄（5周龄）和老年（100周龄）大鼠心脏分离的心内膜内皮细胞（EECs）产生血管活性物质的影响。我们还用Langendorff和工作心脏装置证明了大鼠心脏功能与年龄相关的变化。结果与结论1：剪切应力（0.2 ~ 6dyne/cm）和跨壁压力（0 ~ 150mmHg）可使猪脑膜内皮细胞产生前列环素（PGI）。暴露于8-（二甲氨基）辛基3,4,5 -三甲氧基苯甲酸盐酸盐（一种细胞内钙动员抑制剂）或环吡唑酸（和内质网Ca D12+ d1 - atp酶抑制剂）的细胞，受剪切应力诱导的PGI D22 D2的产生被显著抑制；老年大鼠EECs的产生比幼龄大鼠有所减少。2：大鼠脑脊液细胞的增殖随着年龄的增长而下降，与细胞的形态扩大有关。3：相差电镜显示皮下注射苦杏仁碱诱导右心室肥厚的大鼠右心室脑电图细胞增大。4：大鼠心排血量、主动脉流量、心率随年龄增长明显下降。剪切应力增加了EECs中PGI的生成，剪切应力的机械传导依赖于EECs中钙的动员。大鼠机械转导功能随年龄增长而减弱，右心室脑电图随年龄增长和右心室肥厚而增大。这些结果提示心内膜功能障碍参与心力衰竭的发生发展。

项目成果

Michio Hashimoto et al.: "Effects of eicosapentaenoic acid and docosahexaenoic acid on plasma membrane fluidity of aortic endothelial cells"Lipids. 34. 1297-1304 (1999)

Michio Hashimoto 等人：“二十碳五烯酸和二十二碳六烯酸对主动脉内皮细胞质膜流动性的影响”脂质。

Michio Hashimoto, Kazumasa Shinozuka, Yoko Tanabe, Hossain Md.Shahdat, Shuji Gamoh, Young Mi Kwon, Yasuakira Tanaka, Masaru Kunitomo and Sumio Masumura.: "Long-term supplementation with a high cholesterol diet decreases the release of ATP from the caudal

Michio Hashimoto、Kazumasa Shinozuka、Yoko Tanabe、Hossain Md.Shahdat、Shuji Gamoh、Young Mi Kwon、Yasuakira Tanaka、Masaru Kunitomo 和 Sumio Masumura。：“长期补充高胆固醇饮食会减少尾部 ATP 的释放

Michio Hashimoto, Kazumasa Shinozuka, Shuji Gamoh, Yoko Tanabe, Md.Hossain Shahdat, Young Mi Kwon, Noriaki Hata, Yoshihisa Misawa, Masaru Kunitomo and Sumio Masumura.: "The hypotensive effect of docosahexaenoic acid is associated with the enhanced release

Michio Hashimoto、Kazumasa Shinozuka、Shuji Gamoh、Yoko Tanabe、Md.Hossain Shahdat、Young Mi Kwon、Noriaki Hata、Yoshihisa Misawa、Masaru Kunitomo 和 Sumio Masumura。：“二十二碳六烯酸的降压作用与增强释放有关

Tomoki Hanada,Michio Hashimoto et al.,: "Shear stress enhances prostacyclin release from endocardial endothelial cells."Life Sciences. 66. 215-220 (1999)

Tomoki Hanada、Michio Hashimoto 等人：“剪切应力增强心内膜内皮细胞释放前列环素。”生命科学。

Shahdat Hossain, Michio Hashimoto et al.: "Age-related changes in platelet microviscosity and aggregation in rats"Clinical and Experimental Pharmacology and Physiology. 26. 426-432 (1999)

Shahdat Hossain、Michio Hashimoto 等人：“大鼠血小板微粘度和聚集的年龄相关变化”临床和实验药理学和生理学。