The role of energy metabolic abnormality in cardiac hypertrophy.

能量代谢异常在心脏肥大中的作用。

• 批准号: 14580015
• 负责人: KASUYA Yoshitoshi
• 金额: $ 2.5万
• 依托单位: Chiba University
• 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-14580015/
• 关键词: cardiac hypertrophy; PPAR-α; Fenofibrate; Endothelin(ET)-1; rat cardiomyocytes; aortic banding model; MAP kinases; JNK

We investigated possible roles of PPAR-α activation in ET-1-induced hypertrophy of cultured rat cardiomyocytes and in an in vivo model of cardiac hypertrophy (abdominal aortic banding : AB). Fenofibrate markedly inhibited the ET-1-induced increase in cell size, protein synthesis, expression level of c-Jun and phosphorylation level of c-Jun and JNK. PPAR-α overexpression inhibited ET-1-induced increase in protein synthesis. Fenofibrate significantly inhibited the ET-1-induced ET-1 mRNA expression, which was confirmed by luciferase assay. EMSA revealed that fenofibrate decreased AP-1 binding activity induced by ET-1 or PMA. Fenofibrate-treatment inhibited LV hypertrophy and phenotypic changes in cardiac gene expression in AB rats.

我们研究了PPAR-α激活在ET-1诱导的培养大鼠心肌细胞肥大和在体心肌肥厚模型(腹主动脉缩窄：AB)中的可能作用。非诺贝特显著抑制ET-1诱导的细胞大小、蛋白质合成、c-jun表达水平及c-jun和JNK的磷酸化水平。PPAR-α过表达可抑制ET-1诱导的蛋白质合成增加。非诺贝特显著抑制ET-1诱导的ET-1mRNA表达，荧光素酶活性检测证实了这一点。EMSA显示非诺贝特可降低ET-1或PMA诱导的AP-1结合活性。非诺贝特治疗可抑制AB大鼠左室肥厚和心脏基因表达的表型变化。

项目成果

Yoko Irukayama-Tomobe: "Activation of peroxisome proliferator-activated receptor-α (PPAR-α) decreases endothelin-1-induced p38 Mitogen-activated protein kinase (MAPK) activation in cardiomyocytes."J.Cardiovasc.Pharmacol.. (in press). (2004)

Yoko Irukayama-Tomobe：“过氧化物酶体增殖物激活受体-α (PPAR-α) 的激活可降低心肌细胞中内皮素-1 诱导的 p38 丝裂原激活蛋白激酶 (MAPK) 的激活。”J.Cardiovasc.Pharmacol..（出版中） ）（2004）。

Yoko Irukayama-Tomobe: "Activation of peroxisome proliferator-activated receptor-a (PPAR-α) decreases endothelin-1-induced p38 Mitogen-activated protein kinase (MAPK) activation in cardiomyocytes."J.Cardiovasc.Pharmacol.. (in press). (2004)

Yoko Irukayama-Tomobe：“过氧化物酶体增殖物激活受体-a (PPAR-α) 的激活可降低心肌细胞中内皮素-1 诱导的 p38 丝裂原激活蛋白激酶 (MAPK) 的激活。”J.Cardiovasc.Pharmacol..（出版中） ）（2004）。

Yoko Irukayama-Tomobe, et al.: "Activation of peroxisome proliferator activated receptor-α (PPAR-α) decreases endothelin-1-induced p38 Mitogen-activated protein kinase (MAPK) activation in cardiomyocytes."J.Cardiovasc.Pharmacol. (in press). (2004)

Yoko Irukayama-Tomobe 等人：“过氧化物酶体增殖物激活受体-α (PPAR-α) 的激活可降低心肌细胞中内皮素-1 诱导的 p38 丝裂原激活蛋白激酶 (MAPK) 的激活。”J.Cardiovasc.Pharmacol。 2004）

Yoko Irukayama-Tomobe: "Endothelin-1-induced caidiac hypertrophy is inhibited by activation of peroxisome proliferator-activated receptor-α partly via blockade of c-Jun NH_2-terminal kinase pathway."Circulation. 109. 904-910 (2004)

Yoko Irukayama-Tomobe：“通过阻断 c-Jun NH_2 末端激酶途径，部分通过过氧化物酶体增殖物激活受体 -α 的激活来抑制内皮素 1 诱导的胆汁肥大。”循环。

Yoko Irukayama-Tomobe, et al.: "Endothelin-1-induced cardiac hypertrophy is inhibited by activation of peroxisome proliferator-activated receptor-α partly via blockade of c-Jun NH_2-terminal kinase pathway."Circulation. 109. 904-910 (2004)

Yoko Irukayama-Tomobe 等人：“过氧化物酶体增殖物激活受体-α 的激活部分通过阻断 c-Jun NH_2 末端激酶途径来抑制内皮素 1 诱导的心脏肥大。”循环。 (2004)