Roles of innate immunity in genesis of heart failure

先天免疫在心力衰竭发生中的作用

• 批准号: 14570640
• 负责人: TAKAHASHI Toshiyuki
• 金额: $ 2.56万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570640/
• 关键词: heart failure; innate immunity; Toll-like receptors; cardiac myocytes; angiotensin II; fetal genes; pulmonary hypertension; Ca^<2+> transient; 心室間相互作用; Ca^<2+>transient

The objectives of this study were to investigate roles of innate immunity in the genesis or progression of myocardial dysfunction. Particularly, we tried to elucidate expression and functional significance of toll-like receptors (TLRs) in cardiac myocytes.1. Molecular cloning and expression analysis of the chick TLR2: we have cloned a cDNA that is homologous to mammalian TLR2s in cultured ventricular myocytes from 10-day-old chick embryos (CEVMs). This cDNA has turned out to correspond to the chick TLR2 type 1 (Fukui, et al.). Total TLR2 expression was detected by Northern blotting in the 10-day-old chick hearts and CEVMs.2. Rat angiotenisn II (A-IO) infusion model: Sprague-Dawley rats were injected subcutaneously and continuously with A-LI to create a ventricular hypertrophy/failure model. Fetal gene reprogramming and alteration of Ca^<2+> were observed in the A-Il-infused rats.3. Rat monocrotaline (MCT) infusion model: MCT was also given subcutaneously and continuously to male rats to create pulmonary hypertension and right ventricular failure. Fetal gene reprogramming occurred in both the right and left ventricles, although some differences were observed, suggesting a role of ventricular interaction.4. Measurements of Ca^<2+> in cardiac myocytes: Ca^<2+> transient in cardiac myocytes was recorded with flou-3 or cameleon, which can be expressed specifically in sarcoplasmic reticulum.

本研究的目的是调查先天免疫在心肌功能障碍的发生或进展中的作用。特别是，我们试图阐明Toll样受体(TLRs)在心肌细胞中的表达和功能意义。 1．鸡TLR2的分子克隆和表达分析：我们在10日龄鸡胚胎（CEVM）培养的心室肌细胞中克隆了与哺乳动物TLR2同源的cDNA。该 cDNA 已被证明与小鸡 TLR2 1 型相对应（Fukui 等人）。采用Northern印迹法检测10日龄鸡心脏和CEVM中TLR2总表达。2．大鼠血管紧张素II（A-IO）输注模型：向Sprague-Dawley大鼠皮下持续注射A-LI以创建心室肥厚/衰竭模型。在A-II输注大鼠中观察到胎儿基因重编程和Ca 2+ 改变。 3．大鼠野百合碱（MCT）输注模型：将MCT持续皮下注射给雄性大鼠，以产生肺动脉高压和右心室衰竭。胎儿基因重编程发生在右心室和左心室，尽管观察到一些差异，这表明心室相互作用的作用。4．心肌细胞中Ca 2+ 的测量：用flou-3或cameleon记录心肌细胞中Ca 2+ 瞬时值，flou-3或cameleon可以在肌浆网中特异性表达。

项目成果

Kasai H et al.: "Direct measurement of Ca^<2+> in the SR of living cardiac myocytes."Biochem Biophys Res Commun. 314. 1014-1020 (2004)

Kasai H等人：“直接测量活体心肌细胞SR中的Ca 2+ 。”Biochem Biophys Res Commun。

Yao A, et al.: "Characteristic effects of α_1-β_<1,2>-adrenergic blocking agent, carvedilol, on [Ca^<2+>]_i in ventricular myocytes compared with those of timolol and atenolol."Circ J. 67. 83-90 (2003)

Yao A 等人：“与噻吗洛尔和阿替洛尔相比，α_1-β_<1,2>-肾上腺素能阻断剂卡维地洛对心室肌细胞 [Ca^<2+>]_i 的特征影响。”Circ J . 67. 83-90 (2003)

Kasai H, et al.: "Direct measurement of Ca^<2+> in the SR of living cardiac myocytes."Biochem Biophys Res Commun. 314. 1014-1020 (2004)

Kasai H等人：“直接测量活体心肌细胞SR中的Ca 2+ 。”Biochem Biophys Res Commun。