The monitoring of monocyte glucose metabolism for the prevention of atherosclerosis progression in diabetes

• Project/Area Number: 20K17121
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: University of Miyazaki
• Principal Investigator: Matsuura Yunosuke 宮崎大学, 医学部, 准教授 (40795853)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 糖尿病性動脈硬化 / 免疫代謝連関 / 残余リスク / 血栓止血 / 糖尿病 / 動脈硬化症 / 単球・マクロファージ / インスリン / フレイル / アミノ酸代謝 / 単球 / マクロファージ / 動脈硬化

Outline of Research at the Start

糖尿病は動脈硬化性心血管疾患の強い危険因子であるが、なぜ危険因子となるのかについては未だ分かっていない。本研究では、血液単球における糖代謝を評価し、同代謝に対する糖尿病の影響を検証する。また、観察結果を踏まえてin vitroでメカニズム解析を行う。本研究を通して、糖尿病性動脈硬化症の病態解明と病態に基づく動脈硬化進展予防戦略の構築への貢献を目指す。

Outline of Final Research Achievements

Multilayered and multifaceted studies were conducted to elucidate the pathogenesis of diabetic atherosclerosis, including the following.
①. Pathological, metabolomic, and RNA microarray analyses using human aortic surgery samples and mechanistic analysis of the inflammatory regulation using human peripheral blood mononuclear cell-derived macrophages, ②. Metabolic and proteomic analyses using diabetic mouse macrophages, ③. Vascular metabolism analysis using a rabbit atherosclerotic stent implantation model and mechanistic analysis of thrombus regulation using cultured cells, and ④. Metabolic analysis of amino acids in the blood from diabetic and non-diabetic patients with cardiovascular disease. From the results of the above analyses, we obtained fundamental knowledge for constructing a prevention scheme for the progression of diabetic atherosclerosis.

Academic Significance and Societal Importance of the Research Achievements

糖尿病は、糖代謝のみならず、脂質代謝やアミノ酸代謝等の異常を伴う複合的な代謝異常である。糖尿病が、動脈硬化性心血管疾患の発症及び進展における強いリスク因子である事は疫学上明らかであるが、リスク因子となる基盤病態に関しては不明な点が多い。従って、糖尿病または非糖尿病性動脈硬化症の病態及びその相違点に関する知見の集積は、治療標的を見据えた糖尿病患者における動脈硬化進展予防スキームの構築において必要不可欠と云える。

Research Products

• [Journal Article] JCS/CVIT/JCC 2023 Guideline Focused Update on Diagnosis and Treatment of Vasospastic Angina (Coronary Spastic Angina) and Coronary Microvascular Dysfunction (2023)
  • Author(s): Hokimoto S, Kaikita K, Yasuda S, Tsujita K, et al.
  • Journal Title: Circulation Journal Volume: 87 Issue: 6 Pages: 879-936
  • DOI: 10.1253/circj.CJ-22-0779
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2023-05-25
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between coronary artery calcium score and bleeding events after percutaneous coronary intervention in chronic coronary syndrome (2023)
  • Author(s): Komaki Soichi、Ishii Masanobu、Kaichi Ryota、Takae Masafumi、Mori Takayuki、Toida Reiko、Kurogi Kazumasa、Matsuura Yunosuke、Yamamoto Nobuyasu、Tsujita Kenichi、Tsuruda Toshihiro、Kaikita Koichi
  • Journal Title: Heart and Vessels Volume: - Issue: 7 Pages: 919-928
  • DOI: 10.1007/s00380-023-02248-7
  • Peer Reviewed
• [Journal Article] Optimal Antithrombotic Therapy in Patients Undergoing Percutaneous Coronary Intervention: A Focused Review on High Bleeding Risk (2022)
  • Author(s): Matsuura Yunosuke、Moribayashi Kohei、Kaikita Koichi
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 29 Issue: 10 Pages: 1409-1420
  • DOI: 10.5551/jat.RV17066
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2022-10-01
  • Peer Reviewed
• [Journal Article] Stratifying Bleeding Risk and Beyond ― Predicting Where Bleeding Will Occur ― (2022)
  • Author(s): Moribayashi Kohei、Matsuura Yunosuke、Kaikita Koichi
  • Journal Title: Circulation Journal Volume: 86 Issue: 5 Pages: 784-786
  • DOI: 10.1253/circj.CJ-22-0091
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2022-04-25
  • Peer Reviewed
• [Journal Article] Diabetes Suppresses Glucose Uptake and Glycolysis in Macrophages (2022)
  • Author(s): Matsuura Yunosuke、Shimizu-Albergine Masami、Barnhart Shelley、Kramer Farah、Hsu Cheng-Chieh、Kothari Vishal、Tang Jingjing、Gharib Sina A.、Kanter Jenny E.、Abel E. Dale、Tian Rong、Shao Baohai、Bornfeldt Karin E.
  • Journal Title: Circulation Research Volume: 130 Issue: 5 Pages: 779-781
  • DOI: 10.1161/circresaha.121.320060
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Upregulated Kynurenine Pathway Enzymes in Aortic Atherosclerotic Aneurysm: Macrophage Kynureninase Downregulates Inflammation (2021)
  • Author(s): Nishimura Masanori、Yamashita Atsushi、Matsuura Yunosuke、Okutsu Junichi、Fukahori Aiko、Hirata Tsuyoshi、Nishizawa Tomohiro、Ishii Hirohito、Maekawa Kazunari、Nakamura Eriko、Kitamura Kazuo、Nakamura Kunihide、Asada Yujiro
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 28 Issue: 11 Pages: 1214-1240
  • DOI: 10.5551/jat.58248
  • NAID: 130008110108
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2021-11-01
  • Peer Reviewed / Open Access
• [Journal Article] Intracellular glutamine level determines vascular smooth muscle cell-derived thrombogenicity. (2021)
  • Author(s): Koyama S, Yamashita A, Matsuura Y, Saito Y, Maekawa K, Gi T, Kitamura K, Asada Y
  • Journal Title: Atherosclerosis Volume: 328 Pages: 62-73
  • DOI: 10.1016/j.atherosclerosis.2021.05.012
  • Peer Reviewed / Open Access
• [Presentation] An Autopsy Case of Infective Endocarditis Developing into Aortic Wall Abscess Formation and Aortic Dissection (2023)
  • Author(s): Y.Suiko, R.Matsuura, H.Tanaka, K.Moribayashi, Y.Yamamura, K.Kuroki, Y. Matsuura, T.Ideguchi, T.Ishikawa, T.Tsuruda, T.Kiwaki, Y.Sato, K. Kaikita
  • Organizer: 第87回日本循環器学会学術集会
• [Presentation] Three Cases with High Cardiac Uptake of 99mTc-pyrophosphate but without Histological Proof of Cardiac Transthyretin Amyloidosis (2023)
  • Author(s): K.Yamamoto, H.Tanaka, Y.Matsuura, S.Tomita, H.Shimazu, S.Izumoto, R.Matsuura, Y.Suiko, K.Nagatomo, K.Moribayashi, Y.Yamamura, K.Kuroki, T.Ideguchi, T.Ishikawa, T.Tsuruda, K.Kaikita
  • Organizer: 第87回日本循環器学会学術集会
• [Presentation] The Association of Serum Angiopoietin Like 3 Level with Non-Lipid Clinical Factors and Lipid Parameters in Patients with Cardiovascular Disease (2023)
  • Author(s): H.Tanaka, Y.Suiko, K.Moribayashi, Y.Matsuura, T.Ishikawa and K.Kaikita
  • Organizer: 第87回日本循環器学会学術集会
• [Presentation] Frailty in patients with atherosclerotic cardiovascular disease: frail phenotype, relevant clinical factors, and blood amino acid metabolites (2023)
  • Author(s): K.Moribayashi, Y.Matsuura, H.Shimazu, Y.Suiko, H.Tanaka, T.Ishikawa, K.Kaikita
  • Organizer: 第87回日本循環器学会学術集会
• [Presentation] Impact of Body Mass Index on Blood Pressure in the First-dose Bevacizumab Administration (2023)
  • Author(s): K.Nagatomo, T.Tsuruda, R.Matsuura, Y.Suiko, K.Yamamoto, H.Tanaka, K.Moribayashi, Y.Yamamura, K.Kuroki, Y.Matsuura, T.Ideguchi, T.Ishikawa, J.Kato, K.Kaikita
  • Organizer: 第87回日本循環器学会学術集会