The role of Nicotinamide phosphoribosyltransferase (Nampt) in atrial fibrillation(Fostering Joint International Research)

• Project/Area Number: 15KK0330
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: University of Tsukuba
• Principal Investigator: XU DOONGZHU 筑波大学, 医学医療系, 助教 (20616651)
• Research Collaborator: Chen Peng-Sheng Indiana University School of Medicine, Krannert Institute of Cardiology, 教授 ; Chen Zhenhui Indiana University School of Medicine, Krannert Institute of Cardiology, 准教授 ; Murakoshi Nobuyuki 筑波大学, 医学医療系, 講師
• Project Period (FY): 2016 – 2017
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
• Keywords: 心房細動 / Nampt / カルシウムハンドリング / 肥満 / 加齢 / atrial fibrillation / obesity / hampt / 心臓電気生理 / Nampt/NAD+/Sirtuin系 / カルシウム調節

Outline of Final Research Achievements

Ncotinamide Phosphoribosyltransferase(Nampt) is a rate-limiting NAD+　biosynthetic enzyme known to decrease in adipose tissue of obese and aged rodents and people, Atrial Fibrillation is the most popular arrhythmia in the world and it is highly influenced by the obesity and aging. Nampt+/- mice and high fat diet mice showed increased AF inducibility and increased AF duration time compared to the control group. The mRNA and protein expression of Nampt, Sirt1, ATP2A2, PLN and RYR2 is altered.Conclusion: Nampt inhibition and high fat diet facilitates AF occurrence and increased induced AF duration by altering calcium handling pathway.

Research Products

• [Int'l Joint Research] インディアナ大学医学部Krannert心血管研究センター(米国) (2016)
• [Journal Article] Role of apamin-sensitive small conductance calcium-activated potassium currents in long-term cardiac memory in rabbits (2018)
  • Author(s): Yin Dechun、Chen Mu、Yang Na、Wu Adonis Z.、Xu Dongzhu、Tsai Wei-Chung、Yuan Yuan、Tian Zhipeng、Chan Yi-Hsin、Shen Changyu、Chen Zhenhui、Lin Shien-Fong、Weiss James N.、Chen Peng-Sheng、Everett Thomas H.
  • Journal Title: Heart rhythm Volume: Jan 8
  • DOI: 10.1016/j.hrthm.2018.01.016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts. (2017)
  • Author(s): Yin D, Hsieh YC, Tsai WC, Zhi-Yang Wu A, Jiang Z, Chan YH, Xu DZ, Yang N, Shen C, Chen Z, Lin SF, Chen PS, Everett THt.
  • Journal Title: Circ Arrhythm Electrophysiol Volume: Feb 10(2)
  • DOI: 10.1161/circep.116.004434
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] hospholamban is concentrated in the nuclear envelope of cardiomyocytes and involved in perinuclear/nuclear calcium handling. (2016)
  • Author(s): Wu AZ, Xu D, Yang N, Lin SF, Chen PS, Cala SE, Chen Z.
  • Journal Title: J Mol Cell Cardiol. Volume: 100 Pages: 1-8
  • DOI: 10.1016/j.yjmcc.2016.09.008
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] A Nuclear Pool of Phospholamban in Cardiomyocytes Regulates Nuclear Calcium Cycling Involving Inositol 1,4,5-Trisphosphate Receptor (2018)
  • Author(s): Dongzhu Xu, Mu Chen , Adonis Z. Wu, Evangelia Kranias, Shien-Fong Lin, Peng-Sheng Chen, Zhenhui Chen
  • Organizer: The Heart Rhythm Society’s 39th Annual Scientific Sessions (HRS 2018)
  • Int'l Joint Research
• [Presentation] hospholamban localized to nuclear envelope can be phosphorylated to enhance perinuclear calcium uptake and release (2017)
  • Author(s): DongZhu Xu, Mu Chen, Adonis Z. Wu, Shien-Fong Lin, Peng-Sheng Chen, Zhenhui Chen
  • Organizer: Heart Rhythm 2017
  • Place of Presentation: Chicago, IL. USA
  • Year and Date: 2017-05-10
  • Int'l Joint Research
• [Presentation] Phospholamban localized to nuclear envelope can be phosphorylated to enhance perinuclear calcium uptake and release (2017)
  • Author(s): DongZhu Xu, Mu Chen, Adonis Z. Wu, Evangelia Kranias, Shien-Fong Lin, Peng-Sheng Chen, Zhenhui Chen
  • Organizer: Gordon Research Conferences
  • Place of Presentation: Ventura Beach Marriott, Ventura, CA, United States
  • Year and Date: 2017-02-10
  • Int'l Joint Research
• [Presentation] Nampt deletion increases the vulnerability of Atrial Fibrillation through altering calcium handling pathway in mice. (2017)
  • Author(s): Duo Feng, DongZhu Xu, Murakosi Nobuyuki, Kazuko Tajiri, Taizo Kimura, Akihiko Nogami Kazutaka Aonuma.
  • Organizer: 10th Asia Pacific Heart Rhythm Society Scientific Session (APHRS 2017)
  • Int'l Joint Research
• [Presentation] Phospholamban localized to nuclear envelope can be phosphorylated to enhance perinuclear calcium uptake and release (2017)
  • Author(s): Dongzhu Xu, Mu Chen , Adonis Z. Wu, Shien-Fong Lin, Peng-Sheng Chen, Zhenhui Chen
  • Organizer: The Heart Rhythm Society’s 38th Annual Scientific Sessions (HRS 2017)
  • Int'l Joint Research
• [Presentation] Phospholamban modulates perinuclear/nuclear calcium dynamics in cardiomyocytes (2017)
  • Author(s): Dongzhu Xu, Mu Chen , Adonis Z. Wu, Shien-Fong Lin, Peng-Sheng Chen, Zhenhui Chen
  • Organizer: Gorden Research conference
  • Int'l Joint Research