Severity assessment and prognostic evaluation of idiopathic dilated cardiomyopathy by measurement of soluble LOX-1

• Project/Area Number: 26461064
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Gifu University
• Principal Investigator: AOYAMA Takuma 岐阜大学, 大学院医学系研究科, 非常勤講師 (60422713)
• Co-Investigator(Renkei-kenkyūsha): MINATOGUCHI Shinya 岐阜大学, 大学院医学系研究科, 教授 (20190697) ; SAWAMURA Tatsuya 信州大学, 学術研究院医学系, 教授 (30243033) ; NISHIGAKI Kazuhiko 岐阜大学, 医学部附属病院, 准教授 (60198447) ; TAKEMURA Genzou 朝日大学, 歯学部, 教授 (40283311)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 拡張型心筋症 / LOX-1 / 心不全 / sLOX-1

Outline of Final Research Achievements

Severity assessment of dilated cardiomyopathy (DCM) was examined by measurement of sLOX-1. Concentration of soluble LOX-1 were not correlated with BNP and parameters of echocardiography. Next, we focused a question whether LOX-1 contributes to the pathogenesis of DOX-induced cardiomyopathy. Preserved left ventricular function of LOX-1 knockout (KO) mice compared with those of wild (WT) mice was found after DOX administration. Production of ROS, activation of NF-κB, production of TNF-α, expression of VCAM-1, and leukocyte infiltration were observed less in LOX-1 KO mice than WT mice. On the other hand, decreased expression of sarcometric proteins resulted in smaller diameters of CMs in WT mice than in LOX-1 KO mice. Interestingly, expression of LOX-1 in CMs was much more abundant than that in other cells.
LOX-1 in CMs plays the most important roles in the pathology of DOX-induced cardiomyopathy.

Research Products

• [Journal Article] Deletion of LOX-1 Protects against Heart Failure Induced by Doxorubicin. (2016)
  • Author(s): Yokoyama C, Aoyama T, Ido T, Kakino A, Shiraki T, Tanaka T, Nishigaki K, Hasegawa A, Fujita Y, Sawamura T, Minatoguchi S.
  • Journal Title: PLoS One Volume: 11（5） Issue: 5 Pages: e0154994-e0154994
  • DOI: 10.1371/journal.pone.0154994
  • Peer Reviewed / Open Access / Int'l Joint Research