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

2015 Fiscal Year Final Research Report

• Project/Area Number: 26560391
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied health science
• Research Institution: University 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
• Keywords: コレステロール代謝 / 横紋筋融解症 / スタチン

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.

Free Research Field

代謝学