Role of novel vasoconstrictor coupling factor 6 in the pathogenesis of cardiac hypertrophy and cardiac failure

• Project/Area Number: 20590855
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Hirosaki University
• Principal Investigator: SASAKI Singo Hirosaki University, 大学院・医学研究科, 准教授 (20344591)
• Co-Investigator(Kenkyū-buntansha): OSANAI Tomohiro 弘前大学, 大学院・医学研究科, 准教授 (00169278) ; OKUMURA Ken 弘前大学, 大学院・医学研究科, 教授 (20185549)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: Coupling factor 6 / exercise / transverse aortic constriction / hypertrophy / heart failure / transgenic mouse / Congestive heart failure / pressure overload / SERCA2 / Phospholamban / UCG / Exercise / Acidosis / Salt

Research Abstract

To investigate the influence of coupling factor 6 (CF6) to the progression of cardiac hypertrophy and dysfunction, we subjected CF6-overexpressing transgenic mice (TG) to exercise or persistent pressure overload by transverse aortic constriction (TAC) and compared the results with those in wild type mice (WT). Overexpression of CF6 attenuated exercise-induced physiological cardiac hypertrophy and increase in fractional shortening by down-regulating Akt signaling, whereas it exacerbated pressure overload-induced LV hypertrophy and systolic dysfunction. These suggest that CF6 may contribute to the onset and development of congestive heart failure by the suppression of physiological hypertrophy and the exacerbation of pathological hypertrophy.

Research Products

• [Journal Article] Brain natriuretic peptide is released from human astrocytoma cell line U373MG under hypoxia : A possible role in anti-apoptosis (2011)
  • Author(s): Katoh C, et al
  • Journal Title: J Endocrinol Volume: 208 Pages: 51-57
  • Peer Reviewed
• [Journal Article] Overexpression of coupling factor 6 causes cardiac dysfunction under high salt diet in mice. (2010)
  • Author(s): Ashitate T, Osanai T, Tanaka M, Magota K, Echizen T, Izumiyama K, Yokoyama H, Shibutani S, Hanada K, Tomita H, Okumura K
  • Journal Title: J Hypertens 28 Pages: 2243-2251
  • Peer Reviewed
• [Journal Article] Novel pro-atherogenic molecule coupling factor 6 is elevated in patients with stroke : A possible linkage to homocysteine. (2010)
  • Author(s): Osanai T, Fujiwara N, Sasaki S, Metoki N, Saitoh G, Tomita H, Nishimura T, Shibitani S, Yokoyama H, Konta Y, Magota K, Okumura K
  • Journal Title: Ann Med. 42 Pages: 79-86
  • Peer Reviewed
• [Journal Article] p122 protein enhances intracellular calcium increase to acetylcholine : Its possible role in the pathogenesis of coronary spastic angina. (2010)
  • Author(s): Murakami R, et al
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 10 Pages: 1968-1975
  • Peer Reviewed
• [Journal Article] Overexpression of coupling factor 6 causes cardiac dysfunction under hieh salt diet in mice (2010)
  • Author(s): Ashitate T, et al
  • Journal Title: J Hypertens Volume: 28 Pages: 2243-2251
  • Peer Reviewed
• [Journal Article] Novel pro-atherogenic molecule coupling factor 6 is elevated in patients with stroke : A possible linkage to homocysteine. (2010)
  • Author(s): Osanai T, et al
  • Journal Title: Ann Med 42 Pages: 79-86
  • Peer Reviewed
• [Journal Article] Coupling factor 6 as a novel vasoactive and proatherogenic peptide in vascular endothelial cells. (2009)
  • Author(s): Osanai T, Magota K, Okumura K
  • Journal Title: Naunyn Schmiedebergs Arch Pharmacol. 380 Pages: 205-214
  • Peer Reviewed
• [Journal Article] Coupling factor 6-induced prostacyclin inhibition is enhanced in vascular smooth muscle cells from spontaneously hypertensive rats. (2009)
  • Author(s): Osanai T, Tomita H, Yamada M, Tanaka M, Ashidate T, Echizen T, Katoh C, Magota K, Okumura K
  • Journal Title: J Hypertens 27 Pages: 1823-1828
  • Peer Reviewed
• [Journal Article] Coupling factor 6 enhances Src-mediated responsiveness to angiotensin II in resistance arterioles and cells. (2009)
  • Author(s): Osanai T, Tomita H, Kushibiki M, Yamada M, Tanaka M, Ashitate T, Echizen T, Katoh C, Magota K, Okumura K
  • Journal Title: Cardiovasc Res. 81 Pages: 780-787
  • Peer Reviewed
• [Journal Article] Upregulation of soluble vascular endothelial growth factor receptor type 1 by endogenous prostacyclin inhibitor coupling factor 6 in the vascular endothelial cells : A role of acidosis-induced c-Src activation. (2009)
  • Author(s): Echizen T, Osanai T, Ashitate T, Yokoyama H, Shibutani S, Tanaka M, Tomita H, Koji Magota K, Okumura K
  • Journal Title: Hypertens Res 32 Pages: 182-187
  • NAID: 10024829936
  • Peer Reviewed
• [Journal Article] Generation and characterization of coupling factor 6-overexpressing transgenic mice. (2009)
  • Author(s): Asitate T, Osanai T, Tanaka M, Magota K, Echizen T, Tomita T, Okumura K
  • Journal Title: Hirosaki Medical Journal 60 Pages: 18-26
  • NAID: 110007079176
  • Peer Reviewed
• [Journal Article] Coupling factor 6-induced prostacyclin inhibition is enhanced in vascular smooth muscle cells from spontaneously hypertensive rats. (2009)
  • Author(s): Osanai T, et al
  • Journal Title: J Hypertens 27 Pages: 1823-1828
  • Peer Reviewed
• [Journal Article] Coupling factor 6 as a novel vasoactive and proatherogenic peptide in vascular endothelial cells. (2009)
  • Author(s): Osanai T, et al
  • Journal Title: Naunyn Schmiedebergs Arch Pharmacol 380 Pages: 205-214
  • Peer Reviewed
• [Journal Article] Coupling factor 6 enhances Src-mediated responsiveness to an giotensin II in resistance arterioles and cells (2009)
  • Author(s): Osanai T, et.al.
  • Journal Title: Cardiovasc Res 81 Pages: 780-787
  • Peer Reviewed
• [Journal Article] Upregulation of soluble vascular endothelial growth factor receptor type 1 by endogenous prostacyclin inhibitor coupling factor 6 in the vascular endothelial cells : A role of acidosis-induced c-Src activation (2009)
  • Author(s): Echizen T, Osanai T, et.al.
  • Journal Title: Hypertens Res 32 Pages: 182-187
  • NAID: 10024829936
  • Peer Reviewed
• [Journal Article] Coupling factor 6 downregulates platelet endothelial cell adhesion molecule-1 via c-Src activation and acts as a proatherogenic molecule. (2008)
  • Author(s): Kumagai A, Osanai T, Katoh C, Tanaka M, Tomita H, Morimoto T, Murakami R, Magota K, Okumura K
  • Journal Title: Atherosclerosis. 200 Pages: 45-50
  • Peer Reviewed
• [Journal Article] Coupling factor 6 downregulates platelet endothelial cell adhesion mol ecule-1 via c-Src activation and acts as a oroatherogenic molecule (2008)
  • Author(s): Kumagai A. Osanai T, et.al.
  • Journal Title: Atherosclerosis 200 Pages: 45-50
  • Peer Reviewed
• [Presentation] 新規の細胞内pH調節機構F_1F_o complexはcoupling factor 6で活性化され血圧並びに糖代謝を調節する (2010)
  • Author(s): 長内智宏、渋谷修司、花田賢二、泉山圭、相楽繁樹、山本祐子、奥村謙
  • Organizer: 第33回日本高血圧学会総会
  • Place of Presentation: 福岡
• [Presentation] Coupling factor 6 enhances the action of angiotensin II and causes insulin resistance in mice. (2009)
  • Author(s): 長内智宏, 奥村謙
  • Organizer: Scientific Sessions 2009 (American Heart Association)
  • Place of Presentation: Orland (USA)
• [Presentation] 新規の昇圧物質coupling factor 6はcSrcの活性化を介してangiotensin IIの収縮反応を亢進させる (2009)
  • Author(s): 長内智宏、櫛引基、山田雅大、奥村謙
  • Organizer: 第32回日本高血圧学会総会
• [Presentation] Interaction between coupling factor 6 and ecto F1Fo complex induces hypertension and diabetes by tissue acidosis. (2008)
  • Author(s): 長内智宏, 奥村謙
  • Organizer: Scientific Sessions 2008 (American Heart Association)
  • Place of Presentation: Chicago (USA)
• [Presentation] Overexpression of coupling factor 6 links hypertension to diabetes by c-Src-mediated signaling pathway in mice. (2008)
  • Author(s): Osanai T, Tanaka M, Echizen T, Ashitate T, Tomita H, Okumura K.
  • Organizer: Scientific Sessions 2008 (American Heart Association)
  • Place of Presentation: New Orleans (USA)
• [Presentation] 高血圧と糖尿病の病態形成における細胞内酸性化の意義:Coupling factor 6過剰発現マウスを用いた解析 (2008)
  • Author(s): 長内智宏、芦立俊宗、越前崇、山田雅大、奥村謙
  • Organizer: 第31回日本高血圧学会総会
• [Remarks] ホームページ等