| Project/Area Number |
12557062
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Chiba University |
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Principal Investigator |
KOMURO Issei Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (30260483)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Katsuya Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (10191579)
WAKIMOTO Kouji TANABE SEIYAKU CO., LTD., Researcher, 先端医学研究部, 研究員
YAMAZAKI Tsutomu Tokyo University, Associate Professor, 大学院・医学系研究科, 助教授 (60251245)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2001: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2000: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | NCX / knockout mice / pressure overload / cardiac hypertrophy / diastolic dysfunction / SERCA2 / L-type Ca^<2+> channel / ischemia-reperfusion / Ca^<2+>チャネル / ライアノジン受容体 / カルシウム / 心エコー / Na^+ / Ca^<2+>交換体 / CSX / 細胞内カルシウム |
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| Research Abstract |
The Na^+-Ca^<2+> exchanger (NCX) on the plasma membrane is thought to be the main calcium extrusion system from the cytosol to the extracellular space in many mammalian excitable cells including cardiac myocytes. Three mammalian isoforms of NCX (NCX1, NCX2 and NCX3) have been isolated and NCX1 is expressed at high levels in the heart. However, the pathophysiological role of NCX in the heart is still unclear because of lack of specific inhibitors of NCX. To determine the role of NCX in cardiac contraction and the development of cardiac hypertrophy, we imposed pressure overload on the heart of heterozygous NCX knockout (KO) mice by constricting transverse aorta and examined cardiac function and morphology at three weeks after operation. Although there was no difference in cardiac function between sham-operated KO mice and sham-operated wild type (WT) mice, KO mice showed higher left ventricular pressure, and better systolic function than WT mice in response to pressure overload. Northern blot analysis revealed that mRNA levels of sarcoplasmic reticulum Ca^<2+>-ATPase (SERCA2) were reduced by pressure overload in left ventricles of WT mice but not of KO mice. Hypertrophic changes with interstitial fibrosis were more prominent in KO mice than WT mice. These results suggest that reduction of NCX results in supernormalized cardiac function and causes marked cardiac hypertrophy in response to pressure overload.
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