Effect of minocycline about the inhibition of granulomatous inflammation in cardiac sarcoidosis

• Project/Area Number: 25461064
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Wakayama Medical University
• Principal Investigator: Orii Makoto 和歌山県立医科大学, 医学部, 助教 (70508986)
• Co-Investigator(Kenkyū-buntansha): Akasaka Takashi 和歌山県立医科大学, 医学部, 教授 (70322584) ; Imanishi Toshio 和歌山県立医科大学, 医学部, 研究員 (00285389) ; Hirata Kumiko 和歌山県立医科大学, 医学部, 講師 (10382152)
• Co-Investigator(Renkei-kenkyūsha): Eishi Yoshinobu 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (70151959)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 心サルコイドーシス / 炎症性単球 / ミノサイクリン / 肉芽腫 / FDG-PET / 心臓MRI / 18F FDG PET / 単球サブセット / 18F FDG PET/CT / 副腎皮質ステロイド / アクネ菌 / 単球 / FDG PET

Outline of Final Research Achievements

We aimed to evaluate whether specific monocyte subsets could serve as surrogate markers of disease activity in cardiac sarcoidosis (CS) evaluated by 18F-FDG PET.
We divided the CS patients into 2 groups: known CS receiving corticosteroid therapy (Rx(+)) and new-onset CS (Rx(－)), and analyzed 3 distinct monocyte subsets (CD14+CD16－, CD14++CD16+, and CD14+－CD16+). Monocyte subsets were also analyzed in Rx(－) patients before and 12 weeks after starting corticosteroid therapy. Inflammatory activity was quantified by FDG uptake. The proportion of CD14++CD16+ monocytes in Rx(+) patients was significantly lower than in Rx(－) patients. After corticosteroid therapy, FDG uptake was significantly improved. The proportion of CD14++16+ monocytes showed a significant decrease. The decrease in the proportion of CD14++16+ monocytes significantly correlated with the decrease in FDG uptake.
CD14++16+ monocytes are a possible surrogate marker of the therapeutic effect of corticosteroid therapy in CS.

Research Products

• [Journal Article] The comparison of cardiac magnetic resonance imaging and 18F-fluoro-2-deoxyglucose positron emission tomography manifestations, and regional response to corticosteroid therapy in newly diagnosed cardiac sarcoidosis with complete heart block. (2015)
  • Author(s): Orii M, Hirata K, Tanimoto T, Ota S, Shiono Y, Yamano T, Ino Y, Yamaguchi T, Kubo T, Tanaka A, Akasaka T.
  • Journal Title: Heart rhythm Volume: 12 Issue: 12 Pages: 2477-85
  • DOI: 10.1016/j.hrthm.2015.06.032
  • Peer Reviewed
• [Journal Article] Myocardial Damage Detected by Two-Dimensional Speckle-Tracking Echocardiography in Patients with Extracardiac Sarcoidosis: Comparison with Magnetic Resonance Imaging. (2015)
  • Author(s): Orii M, Hirata K, Tanimoto T, Shiono Y, Shimamura K, Yamano T, Ino Y, Yamaguchi T, Kubo T, Tanaka A, Imanishi T, Akasaka T.
  • Journal Title: J Am Soc Echocardiogr Volume: 印刷中 Issue: 6 Pages: 683-91
  • DOI: 10.1016/j.echo.2015.02.018
  • Peer Reviewed
• [Journal Article] Circulating CD14⁺⁺CD16⁺ Monocyte Subsets as a Surrogate Marker of the Therapeutic Effect of Corticosteroid Therapy in Patients With Cardiac Sarcoidosis (2015)
  • Author(s): Orii M, Imanishi T, Teraguchi I, Nishiguchi T, Shiono Y, Yamano T, Ino Y, Hirata K, Kubo T, Tanaka A, Akasaka T.
  • Journal Title: Circulation Journal Volume: 79 Issue: 7 Pages: 1585-1592
  • DOI: 10.1253/circj.CJ-14-1422
  • NAID: 130005083931
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] β遮断薬投薬を契機に房室伝導障害が顕在化した心サルコイドーシスの１例 (2015)
  • Author(s): 横山真央, 折居 誠, 塩野泰紹, 山野貴司, 松尾好記, 猪野 靖, 山口智由, 平田久美子, 中村 靖, 久保隆史, 田中 篤, 赤阪隆史
  • Journal Title: 心臓 Volume: 47(8) Pages: 1021-27
  • Peer Reviewed
• [Journal Article] Circulating CD14++CD16+ Monocyte Subsets as a Surrogate Marker of the Therapeutic Effect of Corticosteroid Therapy in Patients With Cardiac Sarcoidosis. (2015)
  • Author(s): Orii M, Imanishi T, Teraguchi I, Nishiguchi T, Shiono Y, Yamano T, Ino Y, Hirata K, Kubo T, Tanaka A, Akasaka T.
  • Journal Title: Circulation journal Volume: 印刷中
  • NAID: 130005083931
  • Peer Reviewed / Open Access
• [Journal Article] Assessment of cardiac sarcoidosis with advanced imaging modalities. (2014)
  • Author(s): Orii M, Imanishi T, Akasaka T.
  • Journal Title: Biomed Res Int. Volume: 2014 Pages: 15-15
  • DOI: 10.1155/2014/897956
  • Peer Reviewed / Open Access
• [Presentation] Diagnostic and Therapeutic Utility of Magnetic Resonance-Conditional Pacemaker in Cardiac Sarcoidosis with Complete Heart Block: A Multicenter Clinical Trial (2016)
  • Author(s): Yamamoto Y, Orii M, Tanimoto T, Oota Shingo, Shiono Y, Yamano T, Matsuo Y, Ino Y, Yamaguchi T, Hirata K, Kubo T, Tanaka A, Akasaka T.
  • Organizer: The 80th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2016-03-18
  • Int'l Joint Research
• [Presentation] Clinical utility of the magnetic resonance-conditional pacemaker in patients with A-V nodal block caused by cardiac sarcoidosis. (2014)
  • Author(s): Orii M, Tanimoto T, Oota Shingo, Shiono Y, Yamano T, Matsuo Y, Ino Y, Yamaguchi T, Hirata K, Kubo T, Tanaka A, Akasaka T.
  • Organizer: EUROECHO & other Imaging Modalities
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2014-12-03 – 2014-12-06
• [Presentation] Circulating CD14++CD16+ monocyte subsets as a surrogate marker of inflammatory activity in patients with cardiac sarcoidosis. (2014)
  • Author(s): Orii M, Imanishi T, Teraguchi I, Nisiguchi T, Ozaki Y, Shimamura K, Shiono Y, Yamano T, Tanimoto T, Matsuo Y, Ino Y, Yamaguchi T, Hirata K, Kubo T, Tanaka A, Akasaka T.
  • Organizer: AHA congress
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-11-16 – 2014-11-18
• [Presentation] Circulating CD14++CD16+ monocyte subsets as a surrogate marker of inflammatory activity in patients with cardiac sarcoidosis. (2014)
  • Author(s): Orii M, Imanishi T, Teraguchi I, Nisiguchi T, Ozaki Y, Shimamura K, Shiono Y, Yamano T, Tanimoto T, Matsuo Y, Ino Y, Yamaguchi T, Hirata K, Kubo T, Tanaka A, Akasaka T.
  • Organizer: ESC congress
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2014-08-30 – 2014-09-03
• [Presentation] Inflammatory Change of A-V Nodal Pathway Detected by PET in Cardiac Sarcoidosis Patients with Advanced A-V Nodal Block (2014)
  • Author(s): Orii M, Hirata K, Teraguchi I, Nisiguchi T, Shimokado A, Ozaki Y, Imamura S, Ota S, Shimamura K, Shiono Y, Yamano T, Tanimoto T, Matsuo Y, Ino Y, Yamaguchi T, Kubo T, Tanaka A, Imanishi T, Akasaka T.
  • Organizer: The 78th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Tokyo, Japan
• [Presentation] Early abnormality detected by two-dimensional speckle-tracking echocardiography in patients with extra-cardiac sarcoidosis: comparison with magnetic resonance imaging (2013)
  • Author(s): Orii M, Hirata K, Teraguchi I, Nisiguchi T, Shimokado A, Ozaki Y, Imamura S, Ota S, Shimamura K, Shiono Y, Yamano T, Tanimoto T, Matsuo Y, Ino Y, Yamaguchi T, Kubo T, Tanaka A, Imanishi T, Akasaka T.
  • Organizer: EUROECHO & other Imaging Modalities
  • Place of Presentation: Istanbul, Turkey
• [Presentation] Usefulness of combination of FDG-PET and speckle-tracking echocardiography to predict steroid responders in cardiac sarcoidosis (2013)
  • Author(s): Orii M, Hirata K, Teraguchi I, Nisiguchi T, Shimokado A, Ozaki Y, Imamura S, Ota S, Shimamura K, Shiono Y, Yamano T, Tanimoto T, Matsuo Y, Ino Y, Yamaguchi T, Kubo T, Tanaka A, Imanishi T, Akasaka T.
  • Organizer: EUROECHO & other Imaging Modalities
  • Place of Presentation: Istanbul, Turkey
• [Presentation] Focal inflammation in basal septal portion is related to the development of advanced A-V nodal block in cardiac sarcoidosis (2013)
  • Author(s): Orii M, Hirata K, Yamano T, Tanimoto T, Matsuo Y, Ino Y, Yamaguchi T, Kubo T, Tanaka A, Imanishi T, Akasaka T.
  • Organizer: EUROECHO & other Imaging Modalities
  • Place of Presentation: Istanbul, Turkey
• [Presentation] Focal inflammation in basal septal portion is related to the development of advanced A-V nodal block in cardiac sarcoidosis (2013)
  • Author(s): Orii M, Hirata K, Teraguchi I, Nisiguchi T, Shimokado A, Ozaki Y, Imamura S, Ota S, Shimamura K, Shiono Y, Yamano T, Tanimoto T, Matsuo Y, Ino Y, Yamaguchi T, Kubo T, Tanaka A, Imanishi T, Akasaka T.
  • Organizer: AHA congress
  • Place of Presentation: Dallas, USA
• [Presentation] Usefulness of combination of FDG-PET and speckle-tracking echocardiography to predict steroid responders in cardiac sarcoidosis. (2013)
  • Author(s): Orii M, Hirata K, Teraguchi I, Nisiguchi T, Shimokado A, Ozaki Y, Imamura S, Ota S, Shimamura K, Shiono Y, Yamano T, Tanimoto T, Matsuo Y, Ino Y, Yamaguchi T, Kubo T, Tanaka A, Imanishi T, Akasaka T.
  • Organizer: AHA congress
  • Place of Presentation: Dallas, USA
• [Presentation] Focal inflammation in basal septal portion is related to the development of advanced atrioventricular nodal block in cardiac sarcoidosis (2013)
  • Author(s): Orii M, Hirata K, Tanimoto T, Ishibashi K, Yamano T, Ino Y, Yamaguchi T, Kubo T, Imanishi T, Akasaka T
  • Organizer: ESC congress
  • Place of Presentation: Amsterdam, Netherlands
• [Book] Sarcoidosis: Clinical Manifestations, Diagnostic Methods and Management Strategies (2015)
  • Author(s): Orii M, Akasaka T
  • Total Pages: 35
  • Publisher: Nova Science Publishers
• [Book] Essential Roles of Monocytes/Macrophages in Acute Myocardial Infarction. Myocardial Infarctions: Risk Factors, Emergency Management and Long-Term Health Outcomes (2014)
  • Author(s): Orii M, Imanishi T, Akasaka T
  • Total Pages: 17
  • Publisher: Nova Science Publishers