DPP4 inhibition ameliorates cardiac function by blocking the cleavage of HMGB1 in diabetic mice after myocardial infarction

• Project/Area Number: 15K19390
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Fukushima Medical University
• Principal Investigator: Yuichi Nakamura 福島県立医科大学, 医学部, 博士研究員 (10745798)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: DPP4 inhibitor / Myocardial infarction / HMGB1 / cardiac remodeling / angiogenesis / DPP4 / 心筋梗塞 / 血管新生 / インクレチン / 増殖因子

Outline of Final Research Achievements

DPP4 activity was increased in the diabetic state and blocked by anagliptin administration. The HMGB1 plasma levels were reduced in the diabetic TG compared with the non-diabetic TG mice, but DPP4 inhibition with anagliptin increased HMGB1 plasma levels in the diabetic TG mice. The infarct area was significantly larger in the diabetic TG than in the non-diabetic TG mice, and was reduced by DPP4 inhibition. Cardiac function, angiogenesis, and VEGF expression were impaired in the diabetic TG mice, but ameliorated by the DPP4 inhibition to levels similar to those found in the non-diabetic TG mice.
The DPP4 inhibitor ameliorated cardiac function by inhibiting the inactivation of HMGB1 in diabetic mice after MI.

Research Products

• [Journal Article] DPP4 inhibition ameliorates cardiac function by blocking the cleavage of HMGB1 in diabetic mice after myocardial infarction (2017)
  • Author(s): Akihiko Sato、Yuichi Nakamura
  • Journal Title: International Heart Journal Volume: 印刷中
  • NAID: 130006179202
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The association between circulating anti-angiogenic isoform of vascular endothelial growth factor and clinical profiles in patients with peripheral artery disease. (2016)
  • Author(s): Sato A, Yoshihisa A, Yokokawa T, Shimizu T, Nakamura Y, Misaka T, Kamioka M, Kaneshiro T, Suzuki S, Kunii H, Saitoh S, Takeishi Y
  • Journal Title: International Journal of Cardiology Volume: 207 Pages: 368-369
  • DOI: 10.1016/j.ijcard.2016.01.189
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] High Mobility Group Box 1 Promotes Angiogenesis from Bone Marrow-derived Endothelial Progenitor Cells after Myocardial Infarction (2015)
  • Author(s): Nakamura Y, Suzuki S, Shimizu T, Miyata M, Saitoh S, Kubota I, Takeishi Y
  • Journal Title: J Atheroscler Thromb Volume: in press Issue: 6 Pages: 570-581
  • DOI: 10.5551/jat.27235
  • NAID: 130005078031
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Impact of Peripheral Artery Disease on Prognosis in Hospitalized Heart Failure Patients (2015)
  • Author(s): Nakamura Y, Kunii H, Yoshihisa A, Takiguchi M, Shimizu T, Yamauchi H, Iwaya S, Owada T, Abe S, Sato T, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Sugimoto K, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Journal Title: Circ J Volume: 79 Issue: 4 Pages: 785-793
  • DOI: 10.1253/circj.cj-14-1280 10.1253/circj.CJ-14-1280
  • NAID: 130005130257
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Association of hypocalcemia with mortality in hospitalized patients with heart failure and chronic kidney disease (2015)
  • Author(s): Miura S, Yoshihisa A, Takiguchi M, Shimizu T, Nakamura Y, Yamauchi H, Iwaya S, Owada T, Miyata M, Abe S, Sato T, Suzuki S, Oikawa M, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Journal Title: J Card Fail Volume: 21 Pages: 621-627
  • DOI: 10.1016/j.cardfail.2015.04.015
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Relationship of hyperuricemia with mortality in heart failure patients with preserved ejection fraction (2015)
  • Author(s): Shimizu T, Yoshihisa A, Kanno Y, Takiguchi M, Sato A, Miura S, Nakamura Y, Yamauchi H, Owada T, Abe S, Sato T, Suzuki S, Oikawa M, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 309
  • DOI: 10.1152/ajpheart.00533.2015
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Cardio-protective effects of pentraxin 3 produced from bone marrow-derived cells against ischemia/reperfusion injury (2015)
  • Author(s): Shimizu T, Suzuki S, Sato A, Nakamura Y, Ikeda K, Saitoh S, Misaka S, Shishido T, Kubota I, Takeishi Y
  • Journal Title: J Mol Cell Cardiol Volume: 89 Pages: 306-313
  • DOI: 10.1016/j.yjmcc.2015.10.013
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] DPP4 inhibition ameliorates cardiac function by blocking the cleavage of HMGB1 in diabetic mice after myocardial infarction (2017)
  • Author(s): Akihiko Sato、Yuichi Nakamura
  • Organizer: 第81回日本循環器病学術総会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2017-03-17
• [Presentation] Beneficial impact of dipeptidyl-peptidase-4 inhibitors on mortality of hospitalized heart failure patients with diabetes mellitus. (2016)
  • Author(s): Sato A, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-20
• [Presentation] Hyperuricemia is a prognostic predictor of all-cause mortality in heart failure with preserved ejection fraction. (2016)
  • Author(s): Shimizu T, Yoshihisa A, Takiguchi M, Miura S, Sato A, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-20
• [Presentation] Impact of n-3 polyunsaturated fatty acids on mortality of patients with hospitalized heart failure patients. (2016)
  • Author(s): Watanabe S, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Sato A, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-20
• [Presentation] Prognostic impact of periodic leg movements in hospitalized heart failure patients. (2016)
  • Author(s): Kanno Y, Yoshihisa A, Takiguchi M, Miura S, Sato A, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-20
• [Presentation] The association between plasma level of antiangiogenic isoform of vascular endothelial growth factor and clinical profile of peripheral artery disease. (2016)
  • Author(s): Sato A, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-20
• [Presentation] The CHA2DS2-VASc score predicts high mortality in hospitalized heart failure patients. (2016)
  • Author(s): Watanabe S, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Sato A, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-20
• [Presentation] Associations of insomnia with prognosis in hospitalized heart failure patients. (2016)
  • Author(s): Kanno Y, Yoshihisa A, Takiguchi M, Miura S, Sato A, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-18
• [Presentation] eneficial impact of dipeptidyl-peptidase-4 inhibitors on mortality of patients with hospitalized heart failure patients with diabetes mellitus. (2015)
  • Author(s): Sato A, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] Cardio-protective effects of pentraxin 3 produced from bone marrow-derived cells against ischemia/reperfusion injury. (2015)
  • Author(s): Shimizu T, Suzuki S, Sato A, Nakamura Y, Saitoh S, Mantovani A, Shishido T, Kubota I, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] Impact of n-3 polyunsaturated fatty acids on mortality of patients with hospitalized heart failure patients. (2015)
  • Author(s): Watanabe S, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Sato A, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] Impact of serum uric acid on mortality in heart failure with preserved ejection fraction. (2015)
  • Author(s): himizu T, Yoshihisa A, Takiguchi M, Miura S, Sato A, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] Prognostic impact of periodic leg movements in hospitalized heart failure patients. (2015)
  • Author(s): Kanno Y, Yoshihisa A, Takiguchi M, Miura S, Sato A, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] The association between plasma levels of anti-angiogenic isoform of vascular endothelial growth factor and clinical profiles of peripheral artery disease. (2015)
  • Author(s): Sato A, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] The CHA2DS2-VASc score predicts high mortality in hospitalized heart failure patients. (2015)
  • Author(s): Watanabe S, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Sato A, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] Association between hyperuricemia and mortality in heart failure patients with preserved ejection fraction (2015)
  • Author(s): Shimizu T, Yoshihisa A, Takiguchi M, Miura S, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Takeishi Y.
  • Organizer: 第19回日本心不全学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-10-22
• [Presentation] RCA入口部の高度石灰化亜完全閉塞に対しRotablatorが有効であった症例. (2015)
  • Author(s): 君島勇輔, 國井浩行, 肱岡奈保子, 中村裕一, 阿部諭史, 神山美之, 坂本信雄, 八巻尚洋, 中里和彦, 鈴木 均, 齋藤修一, 竹石恭知
  • Organizer: 第24回日本心血管インターベンション治療学会
  • Place of Presentation: 福岡
  • Year and Date: 2015-07-30
• [Presentation] 心不全患者における末梢動脈疾患の検討. (2015)
  • Author(s): 中村裕一, 國井浩行, 義久精臣, 清水竹史, 大和田卓史, 坂本信雄, 八巻尚洋, 杉本浩一, 中里和彦, 鈴木 均, 齋藤修一, 竹石恭知.
  • Organizer: 第24回日本心血管インターベンション治療学会
  • Place of Presentation: 福岡
  • Year and Date: 2015-07-30
• [Presentation] High mobility group box 1 promotes angiogenesis from bone marrow-derived endothelial progenitor cells after myocardial infarction (2015)
  • Author(s): Yuichi Nakamura, Satoshi Suzuki, Takeshi Shimizu, Shu-ichi Saitoh, Yasuchika Takeishi
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2015-04-24
• [Presentation] Peripheral Artery Disease Predicts Adverse Prognosis of Heart Failure Patients (2015)
  • Author(s): Yuichi Nakamura, Akiomi Yoshihisa, Hiroyuki Kunii, Takeshi Shimizu, Hiroyuki Yamauchi, Satoshi Abe, Satoshi Suzuki, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-ichi Saitoh, Yasuchika Takeishi
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24
• [Presentation] Impact of body mass index on mortality in heart failure patients (2015)
  • Author(s): Takiguchi M, Yoshihisa A, Miura S, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Kobayashi A, Sugimoto K, Yamaki T, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24
• [Presentation] mpact of hypocalcemia on mortality of patients with heart failure and chronic kidney disease (2015)
  • Author(s): Miura S, Yoshihisa A, Takiguchi M, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24
• [Presentation] Impact of insomnia on prognosis in hospitalized heart failure patients (2015)
  • Author(s): Takiguchi M, Yoshihisa A, Miura S, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24
• [Presentation] Impact of peripheral artery disease on prognosis in patients with heart failure (2015)
  • Author(s): Yoshihisa A, Nakamura Y, Kunii H, Takeishi Y
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24
• [Presentation] Impact of serum uric acid on mortality in heart failure with preserved ejection fraction. (2015)
  • Author(s): Shimizu T, Yoshihisa A, Takiguchi M, Miura S, Nakamura Y, Owada T, Yamauchi H, Abe S, Suzuki S, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24
• [Presentation] Myocardial infarct size quantification in mice using pinhole single-photon emission computed tomography. (2015)
  • Author(s): Shimizu T, Nakamura Y, Suzuki S, Kubo H, Ito H, Shishido F, Takenoshita S, Takeishi Y.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24