The anti-inflammatory mechanism of HDL in atherosclerosis

• Project/Area Number: 26670411
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Teikyo University
• Principal Investigator: KONO Hajime 帝京大学, 医学部, 准教授 (60585074)
• Co-Investigator(Kenkyū-buntansha): NANKI Toshihiro 帝京大学, 医学部, 准教授 (00282749) ; 関根 知世子 帝京大学, 医学部, 助教 (40392005)
• Research Collaborator: SEKI Reiko ; YANAGIDA Tamiko
• Project Period (FY): 2014-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 自然炎症 / 動脈硬化 / HDL / ATF3 / TLR

Outline of Final Research Achievements

Recent advances revealed that inflammation plays important roles in the pathogenesis of metabolic syndrome including obesity, diabetes and atherosclerosis. High Density Lipoprotein (HDL) is a strong inhibitor of atherosclerosis, and the level of HDL inversely well correlated with the development of atherosclerosis. The molecular mechanisms HDL to modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. We identified that the transcriptional regulator ATF3, as an HDL-inducible target gene in macrophages that downregulates the expression of Toll-like receptor (TLR)-induced proinflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. We have advanced the field by identifying a specific molecular pathway for anti-inflammatory actions of HDL in macrophages opening up new opportunities for understanding HDL salutary actions and exploiting therapeutic potential.

Research Products

• [Journal Article] High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3. (2014)
  • Author(s): Furukawa H, Kawasaki A, Oka S, Ito I, Shimada K, Sugii S, Hashimoto A, Komiya A, Fukui N, Kondo Y, Ito S, Hayashi T, Matsumoto I, Kusaoi M, Amano H, Nagai T, Hirohata S, Setoguchi K, Kono H, Okamoto A, Chiba N, Suematsu E, Katayama M, Migita K, Suda A, Ohno S, Hashimoto H, Takasaki Y, Sumida T, Nagaoka S, Tsuchiya N, Tohma S
  • Journal Title: Nature Immunology Volume: 9 Pages: 152-160
  • DOI: 10.1371/journal.pone.0087792
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of the contribution of multiple DAMPs and DAMP receptors in cell death-induced sterile inflammatory responses (2014)
  • Author(s): Kataoka H, Kono H, Patel Z, Kimura Y, Rock KL
  • Journal Title: Plos One Volume: 9
  • DOI: 10.1371/journal.pone.0104741
  • Peer Reviewed / Open Access / Acknowledgement Compliant