The effects of calciprotein particles on cardiorenal syndrome

• Project/Area Number: 15K15314
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Jichi Medical University
• Principal Investigator: KANEDA Ruri 自治医科大学, 医学部, 准教授 (70465029)
• Research Collaborator: KURO-O Makoto 自治医科大学, 医学部, 教授 (10716864)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 心腎連関 / 微小リン酸カルシウム結晶 / CPP / 心筋細胞 / Calciprotein particle / Mcp1 / ヒストンH3リシンK4トリメチル化 / 心臓線維芽細胞 / 心筋障害 / 遺伝子発現変化

Outline of Final Research Achievements

The bidirectional disorders between the heart and kidney are focused as “cardiorenal syndrome”. In this project, we investigated the effects of calciprotein particles (CPPs) on cultured cardiomyocytes. We incubated neonatal rat cardiomyocytes with or without synthesized CPPs and performed DNA microarray analysis. In the pathway analysis, CPPs reduced the expression of genes involved in the electron transport chain pathway or the striated muscle contraction pathway. Monocyte chemoattractant protein 1 (Mcp1) gene was up-regulated by CPP stimulation. The transcriptional start site of Mcp1 gene in cardiomyocytes with CPP stimulation was highly enriched with histone H3K4 trimethylation compared with that in cardiomyocytes without CPP.
These data suggest that CPPs might be one of the causative agents for cardiac damage in chronic kidney disease patients and could be a target of therapeutic intervention in cardiorenal syndrome.

Research Products

• [Presentation] The Damage on Cardiomyocytes by Calciprotein Particles (2017)
  • Author(s): Ruri Kaneda, Makoto Kuro-o
  • Organizer: Keystone Symposia on Molecular and Cellular Biology, Epigenetics and Human Disease: Progress from Mechanisms to Therapeutics
  • Place of Presentation: Sheraton Seattle Hotel, Seattle, Washington, USA
  • Year and Date: 2017-01-29
  • Int'l Joint Research