Effects of high-fat diet on pulmonary hypertension and role of MT1-MMP as a biomarker

• Project/Area Number: 18K08080
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Sugimoto Koichi 福島県立医科大学, 医学部, 准教授 (30404867)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 肺高血圧症 / 脂質異常症 / matrix metalloproteinase / 肺高血圧 / matrix metalloprotease / 一酸化窒素 / Smad / 右室肥大 / 血管リモデリング / 脂質代謝異常症 / マトリックスメタロプロテアーゼ

Outline of Final Research Achievements

Eight-week-old female C57 / Bl6 mice were exposed to hypoxia (10% oxygen for 4 weeks) and returned to normal oxygen. They were divided into normal diet (ND) group or high fat diet (HFD) groups and each diet was given for 12 weeks.
As a result, the Fulton index and right ventricular systolic pressure were significantly higher in the HFD group than in the ND group. Medial thickening of the pulmonary artery was more increased in the HFD group. Caspase 3 activity in the lung tissue of the HFD group was reduced, and TUNEL staining showed that apoptosis of pulmonary artery smooth muscle cells was suppressed in the HFD group.
It was also shown that marix metalloprotase is inversely related to right ventricular pressure systolic pressure.

Academic Significance and Societal Importance of the Research Achievements

本研究は肺高血圧症の回復過程における高脂肪食の影響を分子機序的に明らかにし、肺高血圧症の治療戦略の1つとして代謝異常症への介入が重要であることを示した。さらに、血清学的に簡便に肺動脈圧を推定する方法として、血中の膜型1マトリックスメタロプロテアーゼ濃度の測定が有用であり、肺高血圧症の早期診断に役立つ可能性が有ることを示した。

Research Products

• [Presentation] High-fat diet delays pulmonary artery reverse remodeling in mice with hypoxia-induced pulmonary hypertension. (2020)
  • Author(s): 杉本 浩一
  • Organizer: 第84回 日本循環器学会学術集会
  • Int'l Joint Research
• [Presentation] High fat diet delays reverse remodeling of pulmonary artery in hypoxia-induced pulmonary hypertension mice. (2020)
  • Author(s): Koichi Sugimioto
  • Organizer: American Heart Association Scientific Session 2020
  • Int'l Joint Research