Mechanism of Endothelial Dysfunction in Chronic Kidney Disease

• Project/Area Number: 21390249
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kurume University
• Principal Investigator: IMAIZUMI Tsutomu 久留米大学, 医学部, 教授 (60148947)
• Co-Investigator(Kenkyū-buntansha): KAJIMOTO Hidemi 久留米大学, 循環器病研究所, 助教 (50349700) ; KAI Hisashi 久留米大学, 医学部, 准教授 (60281531) ; 安岡 逸 久留米大学, 医学部, 助教 (10461435)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2011: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2010: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2009: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 血管内皮 / 腎不全 / Asymmetric Dimethylarginine / ADMA / 一酸化窒素

Research Abstract

Elevated circulating Asymmetric Dimethylarginine(ADMA) is a cause, not an epiphenomenon, of endothelial dysfunction in chronic kidney disease. This effect is attributable to inhibition of endothelial nitric oxide synthase phosphorylation, which is independent of the competitive inhibition of nitric oxide synthase.

Research Products

• [Journal Article] Inhibition of eNOS Phosphorylation Mediates Endothelial Dysfunction in Renal Failure : New Effect of Asymmetric Dimethylarginine (2012)
  • Author(s): Kajimoto H, Kai H, Imaizumi T(他6人9番目)
  • Journal Title: Kidney International Volume: 81 Issue: 8 Pages: 762-768
  • DOI: 10.1038/ki.2011.476
  • Peer Reviewed
• [Journal Article] Cardiac-specific deletion of SOCS-3 prevents development of left ventricular remodeling after acute myocardial infarction (2012)
  • Author(s): Oba T, Imaizumi T(他14人16番目)
  • Journal Title: J Am Coll Cardiol Volume: 59 Issue: 9 Pages: 838-852
  • DOI: 10.1016/j.jacc.2011.10.887
  • Peer Reviewed
• [Journal Article] Simvastatin prevents large blood pressure variability induced aggravation of cardiac hypertrophy in hypertensive rats by inhibiting RhoA/Ras-ERK pathways (2011)
  • Author(s): Takayama N, Kai H, Imaizumi T(他7人10番目)
  • Journal Title: Hypertens Res Volume: 34 Issue: 3 Pages: 341-347
  • DOI: 10.1038/hr.2010.229
  • NAID: 10031163179
  • Peer Reviewed
• [Journal Article] Enhanced cardiac inflammation and fibrosis in ovariectomized hypertensive rats : a possible mechanism of diastolic dysfunction in postmenopausal women (2011)
  • Author(s): Mori T, Kai H, Imaizumi T(他7人10番目)
  • Journal Title: Hypertens Res Volume: 34 Issue: 4 Pages: 496-502
  • DOI: 10.1038/hr.2010.261
  • NAID: 10031163207
  • Peer Reviewed
• [Journal Article] Augmented neovascularization with magnetized endothelial progenitor cells in rats with hind-limb ischemia (2011)
  • Author(s): Koiwaya H, Imaizumi T(他7人9番目)
  • Journal Title: J Mol Cell Cardiol Volume: 51 Issue: 1 Pages: 33-40
  • DOI: 10.1016/j.yjmcc.2011.03.012
  • Peer Reviewed
• [Journal Article] Low DBP may not be an independent risk for cardiovascular death in revascularized coronary artery disease patients (2011)
  • Author(s): Kai H, Imaizumi T(他5人7番目)
  • Journal Title: J Hypertens Volume: 29 Issue: 10 Pages: 1889-1896
  • DOI: 10.1097/hjh.0b013e32834a5a67
  • Peer Reviewed
• [Journal Article] Plasma aldosterone levels and development of insulin resistance : prospective study in a general population (2011)
  • Author(s): Kumagai E, Imaizumi T(他15人17番目)
  • Journal Title: Hypertension Volume: 58 Issue: 6 Pages: 1043-1048
  • DOI: 10.1161/hypertensionaha.111.180521
  • Peer Reviewed
• [Journal Article] Serum level of pigment epithelium-derived factor is a marker of atherosclerosis in humans (2011)
  • Author(s): Tahara N, Imaizumi T(他8人10番目)
  • Journal Title: Atherosclerosis Volume: 219 Pages: 311-315
  • Peer Reviewed
• [Journal Article] Longest survivor of pulmonary atresia with ventricular septal defect-well-developed major aortopulmonary collateral arteries demonstrated by multidetector computed tomography (2011)
  • Author(s): Fukui D, Kai H, Imaizumi T(他9人12番目)
  • Journal Title: Circulation Volume: 124 Pages: 2155-2157
  • Peer Reviewed
• [Journal Article] Administration of pigment epithelium-derived factor inhibits left ventricular remodeling and improves cardiac function in rats with acute myocardial infarction (2011)
  • Author(s): Ueda S-I, Imaizumi T(他3人5番目)
  • Journal Title: Am J Pathol Volume: 178 Issue: 2 Pages: 591-598
  • DOI: 10.1016/j.ajpath.2010.10.018
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cell-based prostacyclin synthase gene therapy for pulmonary hypertension rats (2010)
  • Author(s): Takemiya K, Kai H, Imaizumi T(他3人6番目)
  • Journal Title: Basic Res Cardiol Volume: 105 Issue: 3 Pages: 409-417
  • DOI: 10.1007/s00395-009-0065-8
  • Peer Reviewed
• [Journal Article] Autologous transplantation of bone marrow mononuclear cells improved ischemic peripheral neuropathy in humans (2010)
  • Author(s): Arima K, Kai H, Imaizumi T(他8人11番目)
  • Journal Title: J Am Coll Cardiol Volume: 56 Issue: 3 Pages: 238-239
  • DOI: 10.1016/j.jacc.2010.02.050
  • Peer Reviewed
• [Journal Article] Target blood pressure for treatment of isolated systolic hypertension in the elderly : Valsartan in elderly isolated systolic hypertension study (2010)
  • Author(s): Ogihara T, Imaizumi T(他12人12番目)
  • Journal Title: Hypertension Volume: 56 Issue: 2 Pages: 196-202
  • DOI: 10.1161/hypertensionaha.109.146035
  • Peer Reviewed
• [Journal Article] Exaggerated blood pressure variability superimposed on hypertension aggravates cardiac remodeling in rats via angiotensin II system-mediated chronic inflammation (2009)
  • Author(s): Kudo H, Kai H, Imaizumi T(他10人13番目)
  • Journal Title: Hypertension Volume: 54 Issue: 4 Pages: 832-838
  • DOI: 10.1161/hypertensionaha.109.135905
  • Peer Reviewed
• [Journal Article] Higher heart rate may predispose to obesity and diabetes mellitus : 20-year prospective study in a general population (2009)
  • Author(s): Shigetoh Y, Imaizumi T(他8人10番目)
  • Journal Title: Am J Hypertens Volume: 22 Issue: 2 Pages: 151-155
  • DOI: 10.1038/ajh.2008.331
  • Peer Reviewed
• [Journal Article] 慢性腎不全患者の心血管病変進展における内因性NO合成阻害物質(ADMA)の役割 (2009)
  • Author(s): 梶本英美、甲斐久史、今泉勉
  • Journal Title: 腎臓 Volume: 32 Pages: 103-107
• [Journal Article] 慢性腎不全患者の心血管病変進展における内因性NO 合成阻害物質(ADMA)の役割 (2009)
  • Author(s): 梶本英美、甲斐久史、今泉勉
  • Journal Title: 腎臓 32 Pages: 103-107
• [Journal Article] Cardiomyocyte-specific transgenic expression of lysyl oxidase-like protein-1 induces cardiac hypertrophy in mice
  • Author(s): Ohmura H, Imaizumi T(他8人10番目)
  • Journal Title: Hypertens Res Volume: (in press)
  • Peer Reviewed
• [Presentation] Inhibition of CaMKII/ERK-mediated eNOS phosphorylation by asymmetric dimethylarginine is novel molecular mechanism of endothelial dysfunction in chronic kidney disease mice (2012)
  • Author(s): Hidemi Kajimoto
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2012-03-16
• [Presentation] Inhibition of CaMKII/ERK-mediated eNOS phosphorylation by asymmetric dimethylarginine is novel molecular mechanism of endothelial dysfunction in chronic kidney disease mice (2012)
  • Author(s): Kajimoto H, Kai H, Aoki H, Yasuoka S, Anegawa T, Imaizumi T
  • Organizer: 76th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Fukuoka, Japan
• [Presentation] Inhibition of CaMKII- and ERK-mediated eNOS phosphorylation impairs endothelial function in renal failure mice : New effect of asymmetric dimethylarginine (2011)
  • Author(s): Hidemi Kajimoto
  • Organizer: American Heart Association's Scientific Sessions
  • Place of Presentation: オーランド
  • Year and Date: 2011-11-15
• [Presentation] Inhibition of CaMKII-and ERK-mediated eNOS phosphorylation impairs endothelial function in renal failure mice : New effect of asymmetric dimethylarginine (2011)
  • Author(s): Kajimoto H, Kai H, Aoki H, Yasuoka S, Anegawa T, Imaizumi T
  • Organizer: American Heart Association's Scientific Sessions
  • Place of Presentation: Orlando
• [Presentation] Increased circulating asymmetric dimethylarginine in chronic kidney disease mice induces endothelial dysfunction by inhibiting Ca/Calmodulin-dependent protein kinase Il-eNOS signaling. (2010)
  • Author(s): 梶本英美
  • Organizer: American Heart Association's Scientific Sessions
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-17
• [Presentation] Asymmetric dimethylarginine impairs endothelial function in CKD mice. (2010)
  • Author(s): 梶本英美
  • Organizer: ISN-Nexus Kyoto 2010
  • Place of Presentation: 京都
  • Year and Date: 2010-04-17
• [Presentation] Smad-Msx2 Pathway Plays an Initial Role in Vascular Calcification in CKD Mice (2010)
  • Author(s): 梶本英美
  • Organizer: 第74回日本循環器学会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-07
• [Presentation] Increased circulating asymmetric dimethylarginine in chronic kidney disease mice induces endothelial dysfunction by inhibiting Ca/Calmodulin-dependent protein kinase II-eNOS signaling (2010)
  • Author(s): Kajimoto H, Kai H, Aoki H, Yasuoka S, Anegawa T, Imaizumi T
  • Organizer: American Heart Association's Scientific Sessions
  • Place of Presentation: Chicago, USA
• [Presentation] 血清Asymmetric Dimethylarginineの増加が腎機能低下における血管内皮障害を起こす (2010)
  • Author(s): Kajimoto H, Kai H, Yasuoka S, Imaizumi T
  • Organizer: 47th Annual Meeting of the Japanese Society of Pediatric Cardiology and Cardiac Surgery Chiba
  • Place of Presentation: Japan
• [Presentation] Asymmetric dimethylarginine triggers vascular dysfunction in CKD mice (2010)
  • Author(s): Kajimoto H, Kai H, Yasuoka S, Imaizumi T
  • Organizer: Xth World Congress of the International Society for Heart Research 2010 Kyoto
  • Place of Presentation: Kyoto, Japan
• [Presentation] Asymmetric dimethylarginine impairs endothelial function in CKD mice (2010)
  • Author(s): Kajimoto H, Kai H, Yasuoka S, Imaizumi T
  • Organizer: ISN-Nexus Symposium 2010
  • Place of Presentation: Kyoto, Japan
• [Presentation] Smad-Msx2 pathway plays an initial role in vascular calcification in CKD mice (2010)
  • Author(s): Kajimoto H, Kai H, Yasuoka S, Anegawa T, Imaizumi T
  • Organizer: 74th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Kyoto, Japan
• [Presentation] Asymmetric Dimethylarginine Triggers Vasculo-Renal Interaction in CKD Mice (2009)
  • Author(s): 梶本英美
  • Organizer: American Heart Association's Scientific Sessions
  • Place of Presentation: Orlando, USA
  • Year and Date: 2009-11-16
• [Presentation] Asymmetric Dimethylarginine is a paracrine regulator of vascular function in CKD (2009)
  • Author(s): 梶本英美
  • Organizer: 第13回心不全学会
  • Place of Presentation: 福岡
  • Year and Date: 2009-10-31
• [Presentation] 腎不全マウスにおける血清 Asymmetric Dimethylazginine の上昇が血管内皮に与える影響 (2009)
  • Author(s): 梶本英美
  • Organizer: 第32回日本高血圧学会
  • Place of Presentation: 滋賀
  • Year and Date: 2009-10-02
• [Presentation] 血清 Asymmetric Dimethylarginin の増加が腎不全マウスにおける内皮機能障害を起こす (2009)
  • Author(s): 梶本英美
  • Organizer: 第57回日本心臓病学会
  • Place of Presentation: 札幌
  • Year and Date: 2009-09-20
• [Presentation] Asymmetric dimethylarginine triggers vasculo-renal interaction in CKD mice (2009)
  • Author(s): Kajimoto H, Kai H, Yasuoka S, Anegawa T, Aoki H, Imaizumi T
  • Organizer: American Heart Association's Scientific Sessions
  • Place of Presentation: Orlando, USA
• [Presentation] 腎不全マウスにおける血清Asymmetric Dimethylarginineの上昇が血管内皮に与える影響 (2009)
  • Author(s): Kajimoto H, Kai H, Yasuoka S, Aoki H, Anegawa T, Imaizumi T
  • Organizer: The 32^<nd> Annual Scientific Meeting of the Japanese Society of Hypertension
  • Place of Presentation: Shiga, Japan
• [Presentation] Asymmetric dimethylarginine is a paracrine regulator of vascular function in CKD (2009)
  • Author(s): Kajimoto H, Kai H, Yasuoka S, Aoki H, Anegawa T, Imaizumi T
  • Organizer: The 13th Annual Scientific Meeting of the Japanese Heart Failure Society
  • Place of Presentation: Fukuoka, Japan
• [Presentation] 「内皮と脈管疾患」腎-血管連関-ADMAによる内皮障害- (2009)
  • Author(s): 甲斐久史
  • Organizer: 第50回日本脈管学会学術集会
  • Place of Presentation: 東京
• [Presentation] 血清Asymmetric Dimethylarginineの増加が腎不全マウスにおける内皮機能障害を起こす (2009)
  • Author(s): Kajimoto H, Kai H, Yasuoka S, Aoki H, Anegawa T, Imaizumi T
  • Organizer: The 57th Annual Scientific Session of the Japanese College of Cardiology
  • Place of Presentation: Sapporo, Japan