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.

我们评估了机械应力（例如剪切应力和跨壁压力）对从猪心脏、幼猪心脏（5 周龄）和老年心脏（100 周龄）分离的心内膜内皮细胞 (EEC) 产生血管活性物质的影响我们还使用 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。结果和结论 1：剪切应力(0.2~6dyne/cm) 和跨壁压力 (0~150mmHg) 增加猪 EEC 中前列环素 (PGID22D2) 的产生，暴露于 8-(二甲基氨基)辛基 3,4,5- 的细胞显着抑制剪切应力诱导的 PGID22D2 产生。三甲氧基苯甲酸酯此外，老年大鼠的 EEC 的产量比年轻大鼠的 EEC 减少。2：大鼠 EEC 的增殖随着年龄的增长而减少，与细胞形态增大有关。3：相差电子显微镜显示右侧的增大心室从皮下注射野百合碱诱导右心室肥大的大鼠心脏中分离出 EEC。4：随着年龄的增长，大鼠的心输出量、主动脉流量和心率显着下降。剪切应力增强了 EEC 中 PGI-D22 的产生，以及剪切应力的机械转导取决于大鼠 EEC 中的钙动员，随着年龄的增长，右心室 EEC 的机械转导会减少。随着年龄的增长和右心室肥大，这些结果表明心内膜参与了心力衰竭的发展。

项目成果

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

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

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。

Haruki Omori, Michio Hashimoto et al.: "Beneficial effects of FK409, a novel nitric oxide donor, on reperfusion injury of rat liver"Transplantation. 66. 579-585 (1998)

Haruki Omori、Michio Hashimoto 等人：“新型一氧化氮供体 FK409 对大鼠肝脏再灌注损伤的有益作用”移植。