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Why did lack of cholesterol in the skeletal muscle cause rhabdomyolysis and sudden death?

Research Project

Project/Area Number 26560391
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Applied health science
Research InstitutionUniversity of Tsukuba

Principal Investigator

Nakagawa Yoshimi  筑波大学, 国際統合睡眠医科学研究機構, 准教授 (80361351)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsコレステロール代謝 / 横紋筋融解症 / スタチン / HMGCR
Outline of Final Research Achievements

To identify the molecular mechanism that statin, a therapeutic agent for dyslipidemia, causes rhabdomyolysis, we generated skeletal muscle specific HMGCR KO (mKO) mice. These mice exhibited deficient of cholesterol synthesis leading to rhabdomyolysis. However, these mice had higher cholesterol contents in skeletal muscle than WT mice. Next, we generated LDLR KO/ mKO mice, which could not synthesize cholesterol de novo and import cholesterol from extracellular system. LDLR KO/ mKO mice had same phenotypes as mKO mice, thereby proposing that there is an unknown mechanism for cholesterol metabolism.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (3 results)

All 2015 Other

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Remarks (2 results)

  • [Journal Article] Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy.2015

    • Author(s)
      Osaki Y, Nakagawa Y, Miyahara S, Iwasaki H, Ishii A, Matsuzaka T, Kobayashi K, Yatoh S, Takahashi A, Yahagi N, Suzuki H, Sone H, Ohashi K, Ishibashi S, Yamada N, Shimano H
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 466(3) Issue: 3 Pages: 536-540

    • DOI

      10.1016/j.bbrc.2015.09.065

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Remarks] 筑波大学 医学医療系 内分泌代謝・糖尿病内科

    • URL

      http://www.u-tsukuba-endocrinology.jp/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 筑波大学 国際統合睡眠医科学研究機構

    • URL

      http://wpi-iiis.tsukuba.ac.jp/japanese/

    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2017-05-10  

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