Relationship between age-related changes in functions of endocardial endothelial cells and heart failure

心内膜内皮细胞功能年龄相关变化与心力衰竭的关系

• 批准号: 08838014
• 负责人: HASHIMOTO Michio
• 金额: $ 1.41万
• 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: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08838014/
• 关键词: Endocardial endothelial cells; Vascular endothelial cells; Aging; Transmural pressure; Nitric Oxide; Prostacycline; Heart failure; Rats; 細胞内Ca^<2+>; 増殖能; 血小板凝集能

We isolated and cultured endocardial endothelial cells (EECs) from young (5-week-old) and aged (100-week-old) rats, to estimate age-related changes in the cell functions. We also estimated physiological functions of EECs, by comparison of EECs with the vascular endothelial cells (VECs), which were isolated from pigs.Results1 : EECs were isolated with collargenase and subcultured on plastic plates coated with the rat type I collagen. The confluent cell monolayr of rat EECs exhibited a typical cobblestone-like morphology. The purity of EECs assayd by uptake of DiI-Ac-LDL and the presence of factor VIII-related antigen, was consistently>95%, as for vascular endothelial cells.2 : Effects of aging on functions of rat EECs. (1) Proliferation and migration tended to decrease with aging. (2) Production of prostaxycline (PGI_2) and nitric oxide (NO) in the cells significantly decreased with aging. When exposing to transmural pressure, PGI_2 production of young rat EECs significantly potentiated, but that of aged rat EECs did not response.3 : Comparison with VECs : (1) Cell growth of EECs and the anti-aggregation property were higher than those of VECs. (2) The rank order of PGI_2 production is left ventricle EECs>right ventricle EECs>pulmonary arterial ECs>coronary arterial and thoracic aortic ECs. (3) The transmural pressure increased PGI_2 production and decreased NO production of EECs.ConclusionThe present experiments indicate age-related attenuation of EEC functions and suggest the participation of the dysfunction in increase of heart failure with advancing age. The physiological roles of EECs were not clarified in this study, since we could not denude ex vivo only the endocardium from rat hole heart. If we can establish the method to remove the endocardium, the roles will be remarkably elucidated.

我们从幼龄大鼠（5周龄）和老年大鼠（100周龄）中分离并培养心内膜内皮细胞（EECs），以估计细胞功能与年龄相关的变化。我们还通过将EECs与从猪身上分离的血管内皮细胞（VECs）进行比较，估计了EECs的生理功能。结果1：用胶原酶分离得到EECs，并在涂有大鼠I型胶原的塑料板上传代培养。大鼠脑脊液的融合细胞单层呈典型的鹅卵石样形态。与血管内皮细胞一样，通过摄取DiI-Ac-LDL和存在因子viii相关抗原来测定EECs的纯度始终为95%。2：衰老对大鼠脑电细胞功能的影响。(1)随着年龄的增长，细胞的增殖和迁移有减少的趋势。(2)随着年龄的增长，前列腺素（PGI_2）和一氧化氮（NO）的生成显著降低。暴露于跨壁压力时，幼龄大鼠脑脊液中PGI_2的产生显著增强，而老年大鼠脑脊液中PGI_2的产生无反应。3：与VECs的比较：(1)EECs的细胞生长和抗聚集性能均高于VECs。(2) PGI_2的产生顺序为左心室EECs>右心室EECs>肺动脉ECs>冠状动脉和胸主动脉ECs。(3)跨壁压力增加了EECs的PGI_2产量，降低了NO产量。结论脑电图功能随年龄的增长而衰减，提示脑电图功能障碍参与了老年心力衰竭的增加。由于我们不能在体外仅从大鼠空穴心脏中剥离心内膜，因此本研究未明确脑电图细胞的生理作用。如果我们能建立去除心内膜的方法，其作用将得到显著的阐明。

项目成果

佐々木 哲也 外: "心内膜内皮細胞に及ぼす硝酸薬の影響" Therapeutic Research. 18. 18-21 (1997)

Tetsuya Sasaki 等：“硝酸盐药物对心内膜内皮细胞的影响”治疗研究。18. 18-21 (1997)。

Ku K.et al.: "Role of hydroxyl radical scavenger(nicaraven)in recovery of cardiac function following preservation and reperfusion." Tranplantation. 62. 1090-1095 (1996)

Ku K.等人：“羟自由基清除剂（尼卡拉文）在保存和再灌注后心脏功能恢复中的作用。”

Kazumasa Shinozuka, Michio Hashimoto, Young Mi Kwon, Sumio Masumura, Richard A.Bjur, David P.Westfall, aand Masaru Kunitomo.: "Regional differences in noradrenaline-stimulated release of adenosine triphosphate from vascular endothelium." Journal of Smooth

Kazumasa Shinozuka、Michio Hashimoto、Young Mi Kwon、Sumio Masumura、Richard A.Bjur、David P.Westfall、a 和 Masaru Kunitomo.：“去甲肾上腺素刺激血管内皮释放三磷酸腺苷的区域差异。”

Mohd.Shah Alam, Kwansong Ku, Michio Hashimoto, Seishi Nosaka, Yuhei Saitoh, Masanobu Yamauchi, Sumio Masumura, Kengo Nakayama, and Katsuhiro Tamura: "Hydroxyl radical scavenging effect of nicaraven in myocardial and coronary endothelial preservation and r

Mohd.Shah Alam、Kwansong Ku、Michio Hashimoto、Seishi Nosaka、Yuhei Saitoh、Masanobu Yamauchi、Sumio Masumura、Kengo Nakayama 和 Katsuhiro Tamura：“尼卡拉文在心肌和冠状动脉内皮保存和治疗中的羟基自由基清除作用

Yuhei Saitoh, Kwansong Ku, Michio Hashimoto, Seikon Kin, Seishi Nosaka, Sumio Masumura, Kengo Nakayama, and Katsuhiro Tamura: "Which injury is the most important for rat heart preservation ; Flush, cold storage, and/or reperfusion injury ? - Especially th

Yuhei Saitoh、Kwansong Ku、Michio Hashimoto、Seikon Kin、Seishi Nosaka、Sumio Masumura、Kengo Nakayama 和 Katsuhiro Tamura：“哪种损伤对于大鼠心脏保存最重要；冲洗、冷藏和/或再灌注损伤？ - 特别是