A novel therapeutic strategy for atherosclerotic diseases by regulating developmental gene expression in perivascular adipose tissue

• Project/Area Number: 24591120
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: YAMADA Hiroyuki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (00240036)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 動脈硬化 / 胎児プログラミング / 血管周囲脂肪 / マクロファージ / 炎症 / 脂肪細胞 / 肥満

Outline of Final Research Achievements

Maternal obesity elicits metabolic disorders of offspring via epigenetic remodeling of visceral adipose tissue; however, its effect on atherogenesis remains undefined. Here we examined phenotypic alterations in offspring adipose tissue by maternal high-fat diet and investigated their roles in atherosclerosis development. Maternal high-fat diet accelerated atherosclerosis development in adult offspring, in which thoracic periaortic adipose tissue-specific exaggerated accumulation of macrophages and subsequent increase in proinflammatory cytokines expression were involved substantially. Thoracic periaortic adipose tissue specific increased expression of macrophage colony stimulating factor during early development is likely to initiate an inflammatory response by promoting the migration or differentiation/proliferation of monocytes. These data provide a unique opportunity to develop the therapeutic strategy in the prevention of atherosclerotic cardiovascular disease.

Research Products

• [Journal Article] Maternal High-Fat Diet Exaggerates Atherosclerosis in Adult Offspring by Augmenting Periaortic Adipose Tissue-Specific Proinflammatory Response (2015)
  • Author(s): Noriyuki Wakana, Daisuke Irie, Masakazu Kikai, Kensuke Terada, Keita Yamamoto, Hiroyuki Kawahito, Taku Kato, Takehiro Ogata, Tomomi Ueyama, Satoaki Matoba, Hiroyuki Yamada
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 35 Issue: 3 Pages: 558-569
  • DOI: 10.1161/atvbaha.114.305122
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Periaortic adipose tissue-specific activation of the renin-angiotensin system contributes to atherosclerosis development in uninephrectomized apoE-/- mice. (2013)
  • Author(s): 25. Kawahito H, Yamada H, Irie D, Kato T, Akakabe Y, Kishida S, Takata H, Wakana N, Ogata T, Ikeda K, Ueyama T, Matoba S, Mori Y, Matsubara H.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 305 Issue: 5 Pages: 667-675
  • DOI: 10.1152/ajpheart.00053.2013
  • Peer Reviewed
• [Presentation] Maternal high-fat diet exaggerates atherosclerosis development in adult offspring by augmenting periaortic adipose tissue-specific proinflammatory response. (2014)
  • Author(s): Wakana N, Irie D, Kikai M, Terada K, Yamamoto Y, Kato T, Kawahito H, Yamada H.
  • Organizer: American Heart Association Scientific Session 2014
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-11-16 – 2014-11-19
• [Presentation] Transplantation of high-cholesterol diet-induced inflammatory periaortic adipose tissue exaggerates atherosclerosis development in recipient apoE deficient mice. (2013)
  • Author(s): 30. Irie D, Wakana N, Kikai M, Kato T, Kishida S, Kawahito H, Yamada H.
  • Organizer: American Heart Association
  • Place of Presentation: Dallas, USA
• [Presentation] Maternal high-fat diet exaggerates atherosclerosis development in adult offspring by augmenting macrophage proinflammatory response in periaortic adipose tissue. (2013)
  • Author(s): 31. Wakana N, Irie D, Kikai M, Kato T, Kawahito H, Kishida S, Fukai K, Yamada H.
  • Organizer: American Heart Association
  • Place of Presentation: Dallas, USA
• [Presentation] Periaortic adipose tissue-specific activation of renin angiotensin system along with the adipocytes differentiation contributes to atherosclerosis in apoE-/- mice. (2012)
  • Author(s): 28. Irie D, Yamada H, Kato T, Kawahito H, Kishida S, Wakana N, Kensuke Fukui, Kouji Ikeda, Mitsuhiko Okigaki, Hiroaki Matsubara.
  • Organizer: American Heart Association Scientific Session
  • Place of Presentation: Los Angeles, USA
• [Presentation] Transplantation of Periaortic Adipose Tissue from Angiotensin Receptor Blocker-treated Mice Markedly Ameliorates Atherosclerosis Development by Reducing Systemic Inflammatory State.
  • Author(s): 59. 入江大介、若菜紀之、鬼界雅一、加藤拓、岸田聡、川人浩之、山田浩之
  • Organizer: 第78回日本循環器学会
  • Place of Presentation: 東京
• [Presentation] Transplantation of Periaortic Adipose Tissue from High-fat Diet-induced Obese Mice Exaggerates Atherosclerosis Development in Recipient apoE Deficient Mice.
  • Author(s): 60. 鬼界雅一、若菜紀之、入江大介、加藤拓、岸田聡、川人浩之、福居顕介、山田浩之
  • Organizer: 第78回日本循環器学会
  • Place of Presentation: 東京
• [Presentation] Maternal High-fat Diet Exaggerates Atherosclerosis Development in Adult Offspring by Augmenting Macrophage Proinflammatory Response in Periaortic Adipose Tissue.
  • Author(s): 61. 若菜紀之、入江大介、鬼界雅一、加藤拓、川人浩之、岸田聡、福居顕介、山田浩之
  • Organizer: 第78回日本循環器学会
  • Place of Presentation: 東京