Assessment of cardioprotective effect of PDE3A against chronic heart failure

• Project/Area Number: 25860613
• 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: OIKAWA Masayoshi 福島県立医科大学, 医学部, 助教 (30457775)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Phosphodiesterase / Angiotensin II / Isoproterenol / 酸化ストレス / ホスホジエステラーぜ / 心筋線維化 / 心筋肥大 / TGF-β / 虚血再灌流障害

Outline of Final Research Achievements

We used cardiospecific PDE3A overexpression (PDE3TG) mice to the study. Ischemia-reperfusion injury was subjected to PDE3TG or wild-type (WT) mice. PDE3TG mice showed smaller myocardial infarction area than WT mice. A number of apoptotic cariomyocytes were lower in PDE3TG mice. We also performed angiotensin II stimulation. PDE3TG mice displayed inhibited cardiac hypertrophy and fibrosis compared to WT mice. The expression levels of transforming growth factor β, which was increased in WT mice after angiotensin II stimulation, was inhibited in PDE3TG mice. Finally we performed Isoproterenol stimulation. PDE3TG mice showed inhibited cardiac hypertrophy compared to WT mice. 8-OHDG positive area, which indicates oxidative damage, was increased in WT mice heart after isoproterenol stimulation, but not in PDE3TG mice heart. Sirt1 protein expression levels were increased in PDE3TG heart. Thus, we conclude PDE3A has cardioprotective effects through various mechanisms.

Research Products

• [Journal Article] Phosphodiesterase 3A1 Protects the Heart Against Angiotensin II–induced Cardiac Remodeling Through Regulation of Transforming Growth Factor-<i>β</i> Expression (2014)
  • Author(s): Iwaya S, Oikawa M, Yan C, Takeishi Y
  • Journal Title: International Heart Journal Volume: 55 Issue: 2 Pages: 165-168
  • DOI: 10.1536/ihj.13-268
  • NAID: 130003392078
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed / Open Access
• [Journal Article] Cardiovascular function and prognosis of patients with heart failure coexistent with chronic obstructive pulmonary disease (2014)
  • Author(s): Yoshihisa A, Takiguchi M, Shimizu T, Nakamura Y, Yamauchi H, Iwaya S, Owada T, Abe S, Sato T, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Journal Title: J Cardiol Volume: (in press) Issue: 4 Pages: 256-264
  • DOI: 10.1016/j.jjcc.2014.02.003
  • Peer Reviewed
• [Journal Article] Cyclic nucleotide phosphodiesterase 3A1 protects the heart against ischemia-reperfusion injury (2013)
  • Author(s): Oikawa M, Wu M, Lim S, Knight W, Miller C, Cai Y, Lu Y, Blaxall B, Takeishi Y, Abe J, Yan C
  • Journal Title: Journal of Molecular and Cellular Cardiology Volume: 64 Pages: 11-19
  • DOI: 10.1016/j.yjmcc.2013.08.003
  • Peer Reviewed
• [Journal Article] Soluble amyloid precursor protein 770 is a novel biomarker candidate for acute coronary syndrome (2013)
  • Author(s): Kitazume S, Yoshihisa A, Yamaki T, Oikawaa M, Tachida Y, Ogawa K, Imamaki R, Takeishi Y, Yamamoto N, Taniguchi N
  • Journal Title: Proteomics Clinical Applications Volume: 7 Issue: 9-10 Pages: 657-663
  • DOI: 10.1002/prca.201200135
  • Peer Reviewed
• [Presentation] Phoshodiesterase 3A1 protects the heart against isoproterenol-induced cardiac injury via anti-oxidative mechanism (2014)
  • Author(s): Masayoshi Oikawa, Shoji Iwaya, Shu-ichi Saitoh, Yasuchika Takeishi
  • Organizer: The 31st Annual Meeting of the International Society for Heart Research (ISHR) Japanese Section
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2014-12-28 – 2014-12-29
• [Presentation] The usefulness of combined assessment of E/e’ ratio and transmitral flow pattern to interpret cardiac condition (2014)
  • Author(s): Masayoshi Oikawa, Atsushi Kobayashi, Hiroyuki Yamauchi, Satoshi Suzuki, Akiomi Yoshihisa, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-ichi Saitoh, Yasuchika Takeishi
  • Organizer: Scientific Sessions of American Heart Association 2014
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] 心膜下脂肪厚は冠動脈病変と関連する -心エコー法と心臓CTによる比較検討-
  • Author(s): 及川雅啓, 小林 淳, 大和田卓史, 山内宏之, 三阪智史, 竹石恭知
  • Organizer: 第24回 日本心エコー図学会学術集会
  • Place of Presentation: 東京
• [Presentation] 心膜下脂肪厚は冠動脈病変と関連する -心エコー法と心臓CTによる比較検討-
  • Author(s): 大和田卓史, 及川雅啓, 山内宏之, 待井宏文, 三阪智史, 八巻尚洋, 杉本浩一, 国井浩行, 中里和彦, 鈴木 均, 斎藤修一, 竹石恭知
  • Organizer: 第156回 日本循環器学会東北地方会
  • Place of Presentation: 盛岡市
• [Presentation] MDCTが極めて有用であったunroofed coronary sinusの症例
  • Author(s): 神雄一郎, 杉本浩一, 坂本信雄, 鈴木 聡, 佐藤彰彦, 及川雅啓, 鈴木史雄, 鈴木 均, 斎藤修一, 竹石恭知
  • Organizer: 第156回 日本循環器学会東北地方会
  • Place of Presentation: 盛岡市
• [Presentation] Solubule smyloid precrsor protein 770 is secreted in a O-glycosylated form from inflamed endothelial cells
  • Author(s): Kitazume S, Yoshihisa A, Yamaki T, Oikawa M, Tachida Y, Ogawa K, Imamaki R, Hagiwara Y, Kinoshita N, Takeishi Y, Iwata N, Saido T, Yamamoto N, Taniguchi N
  • Organizer: 22nd International Symposium on Glycoconjugates
  • Place of Presentation: Dalian, China
• [Presentation] Phosphodiesterase 3A1 protects the heart against angiotensin II-induced cardiac remodeling via regulating interaction between β-adrenergic and angiotensin II pathways
  • Author(s): Oikawa M, Iwaya S, Yan C, Takeishi Y
  • Organizer: The 30th Annual Meeting of the International Society for Heart Research (ISHR) Japanese Section
  • Place of Presentation: San Diego, USA
• [Presentation] Possible multiple organ damages in patients with peripheral arterial disease
  • Author(s): Nakamura Y, Kunii H, Masuda A, Mizukami H, Oikawa M, Suzuki H, Saitoh S, Takeishi Y
  • Organizer: 第22回 日本心血管インターベンション治療学会学術集会
  • Place of Presentation: 神戸市
• [Presentation] 部分上行大動脈置換術７年後に急性上行大動脈解離を合併し、左冠動脈主幹部閉塞による急性心筋梗塞を生じた一例
  • Author(s): 國分知樹, 國井浩行, 中村裕一, 水上浩行, 及川雅啓, 坂本信雄, 八巻尚洋, 中里和彦, 鈴木 均, 斎藤修一, 竹石恭知
  • Organizer: 第34回 日本心血管インターベンション治療学会東北地方会
  • Place of Presentation: 秋田市
• [Presentation] 心膜下脂肪厚は冠動脈病変と関連する -心エコー法と心臓CTによる比較検討-
  • Author(s): 及川雅啓, 小林 淳, 大和田卓史, 山内宏之, 宮田真希子, 三阪智史, 待井宏文, 斎藤修一, 竹石恭知
  • Organizer: 第61回 日本心臓病学会学術集会
  • Place of Presentation: 熊本市
• [Presentation] 感染性心内膜炎患者における術後抗生剤投与と炎症マーカーの関連性の検討
  • Author(s): 小林 淳, 及川雅啓, 中里和彦, 鈴木 均, 斎藤修一, 竹石恭知
  • Organizer: 第61回 日本心臓病学会学術集会
  • Place of Presentation: 熊本市
• [Presentation] Successful percutaneous coronary intervention for acute myocardial infarction due to compression of left main trunk by a false lumen of acute ascending-aortic dissection seven years after partial ascending-aorta replacement and aortic valve replacement
  • Author(s): Kunii H, Kokubun T, Nakamura Y, Mizukami H, Oikawa M, Suzuki H, Saitoh S, Takeishi Y
  • Organizer: Transcatheter Cardiovascular Therapeutics (TCT) 2013
  • Place of Presentation: San Francisco, CA, USA
• [Presentation] Liver dysfunction assessed by model of end-stage liver disease excluding INR (MELD-XI) scoring system predicts adverse prognosis in heart failure
  • Author(s): Shimizu T, Yoshihisa A, Takiguchi M, Yamauchi H, Owada T, Iwaya S, Miyata M, Sato T, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Organizer: Scientific Sessions of American Heart Association 2013
  • Place of Presentation: Dallas, Texas, USA
• [Presentation] Cardiac function in heart failure patients with chronic obstructive pulmonary diseases（COPD を合併した心不全患者における心機能に関する検討）
  • Author(s): Abe S, Yoshihisa A, Yamauchi H, Owada T, Miyata M, Sato T, Suzuki S, Oikawa M, Kobayashi A, Takeishi Y
  • Organizer: 第17回 日本心不全学会学術集会
  • Place of Presentation: さいたま市
• [Presentation] Cardiac function in heart failure patients with periodic leg movements
  • Author(s): Takiguchi M, Yoshihisa A, Shimizu T, Yamauchi H, Miyata M, Sato T, Suzuki S, Oikawa M, Kobayashi A, Takeishi Y
  • Organizer: 第17回 日本心不全学会学術集会
  • Place of Presentation: さいたま市
• [Presentation] 肝機能障害は心不全の独立した予後不良因子である-MELD-XIスコアによる検討
  • Author(s): 阿部諭史, 義久精臣, 滝口 舞, 清水竹史, 山内宏之, 大和田卓史, 岩谷章司, 宮田真希子, 佐藤崇匡, 鈴木 聡, 及川雅啓, 小林 淳, 八巻尚洋, 杉本浩一, 国井浩行, 中里和彦, 鈴木 均, 斎藤修一, 竹石恭知
  • Organizer: 第157回 日本循環器学会東北地方会
  • Place of Presentation: 仙台市
• [Presentation] アドリアマイシン心筋障害の改善に伴い肺体血流比が変化した心房中隔欠損症の一例
  • Author(s): 滝口 舞, 及川雅啓, 清水竹史, 鈴木 聡, 八巻尚洋, 国井浩行, 杉本浩一, 中里和彦, 鈴木 均, 斎藤修一, 竹石恭知
  • Organizer: 157回 日本循環器学会東北地方会
  • Place of Presentation: 仙台市
• [Presentation] 繰り返す血栓閉塞病変に対してアルガトロバン投与が有効であった一例
  • Author(s): 八巻尚洋, 神雄一朗, 國分知樹, 鈴木 聡, 及川雅啓, 坂本信雄, 杉本浩一, 國井浩行, 中里和彦, 竹石恭知
  • Organizer: 第35回 日本心血管インターベンション治療学会東北地方会
  • Place of Presentation: 郡山市
• [Presentation] Epicardial adipose tissue reflects the presence of coronary artery disease: comparison with abdominal visceral adipose tissue
  • Author(s): Oikawa M, Owada T, Yamauchi H, Misaka T, Takeishi Y
  • Organizer: 第78回 日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] Sleep-disordered breathing exacerbates ongoing myocardial damage in patients with heart failure
  • Author(s): Takiguchi M, Yoshihisa A, Shimizu T, Yamauchi H, Owada T, Iwaya S, Nakamura Y, Miyata M, Abe S, Sato T, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Organizer: 第78回 日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] Model of end-stage liver disease excluding INR (MELD-XI) scoring system for liver function predicts adverse prognosis in heart failure
  • Author(s): Abe S, Yoshihisa A, Takiguchi M, Shimizu T, Yamauchi H, Owada T, Iwaya S, Miyata M, Satoh T, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Organizer: 第78回 日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] Cardio-vascular function in heart failure patients with periodic leg movements
  • Author(s): Takiguchi M, Yoshihisa A, Shimizu T, Yamauchi H, Owada T, Iwaya S, Nakamura Y, Miyata M, Abe S, Satoh T, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Organizer: 第78回 日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] Cardiovascular function and prognosis of patients with heart failure coexistent with chronic obstructive pulmonary disease
  • Author(s): Yoshihisa A, Takiguchi M, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Iwaya S, Miyata M, Abe S, Satoh T, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Organizer: 第78回 日本循環器学会学術集会
  • Place of Presentation: 東京