Effect of statins on endothelial dysfunction and increased vascular oxidative stress in rat arthritis model

• Project/Area Number: 19591191
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kawasaki Medical School
• Principal Investigator: MORITA Yoshitaka Kawasaki Medical School, 医学部, 講師 (50346441)
• Co-Investigator(Kenkyū-buntansha): SATOH Minoru 川崎医科大学, 医学部, 講師 (70449891) ; 矢田 豊隆 川崎医科大学, 医学部, 講師 (00210279)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 関節リウマチ / アジュバント / 関節炎 / 関節炎モデル / スタチン / 内皮機能 / 活性酸素 / 炎症 / 血管障害 / アジュバント関節炎

Research Abstract

関節リウマチ患者では全身に及ぶ炎症により血管も障害を受けており、心筋梗塞や脳卒中などの発症率が高いが、その対策は確立していない。本研究では、高脂血症の薬として広く用いられているスタチンが、ラットの実験的関節炎モデルにおいて、血管の酸化ストレスを軽減させ、血管保護作用を有することを初めて明らかにした。これはリウマチ患者の心血管イベント抑制を目的としたスタチンの有用性に一つの科学的根拠を与えるものである。

Research Products

• [Journal Article] Efficacy of low-dose tacrolimus added to methotrexate in patients with rheumatoid arthritis in Japan : a retrospective study (2008)
  • Author(s): Morita Y (他5名1番目)
  • Journal Title: Mod Rheumatol 18 Pages: 379-84
  • NAID: 10021946978
  • Peer Reviewed
• [Journal Article] Blockade of serotonin 2A receptor improves glomerular endothelial function in rats with streptozotocin-induced diabetic nephropathy (2008)
  • Author(s): Kobayashi S, Satoh M (他8名2番目)
  • Journal Title: Clin Exp Nephrol 12 Pages: 119-25
  • NAID: 10025352144
  • Peer Reviewed
• [Journal Article] Olmesartan ameliorates progressive glomerular injury in subtotal nephrectomized rats through suppression of superoxide production (2008)
  • Author(s): Fujimoto S, Satoh M (他8名2番目)
  • Journal Title: Hypertens Res 31 Pages: 305-13
  • NAID: 10024359991
  • Peer Reviewed
• [Journal Article] Angiotensin II type 1 receptor blocker ameliorates uncoupled endothelial nitric oxide synthase in rats with experimental diabetic nephropathy (2008)
  • Author(s): Satoh M (他8名1番目)
  • Journal Title: Nephrol Dial Transplant 31 Pages: 3806-13
  • Peer Reviewed
• [Journal Article] Pioglitazone enhances the antihypertensive and renoprotective effects of candesartan in Zucker obese rats fed a high-protein diet (2008)
  • Author(s): Namikoshi T, Satoh M (他6名3番目)
  • Journal Title: Hypertens Res 31 Pages: 745-55
  • NAID: 10021934851
  • Peer Reviewed
• [Journal Article] Role of Cu,Zn-SOD in the synthesis of endogenous vasodilator hydrogen peroxide during reactive hyperemia in mouse mesenteric microcirculation in vivo (2008)
  • Author(s): Yada T (他8名1番目)
  • Journal Title: Am J Physiol 294
  • Peer Reviewed
• [Journal Article] Efficacy of low-dose tacrolimus added to methotrexate in patients with rheumatoid arthritis in Japan : a retrospective study (2008)
  • Author(s): Yoshitaka Morita
  • Journal Title: Modern Rheumatology 18 Pages: 379-384
  • NAID: 10021946978
  • Peer Reviewed
• [Journal Article] Fluvastatin reverses endothelial dysfunction and increased vascular oxidative stress in rat adjuvant-induced arthritis (2007)
  • Author(s): Haruna Y, Morita Y, Yada T, Satoh M, Fox DA, Kashihara N
  • Journal Title: Arthritis Rheum 56 Pages: 1827-35
  • Peer Reviewed
• [Journal Article] Anti-tumor necrosis factor therapy increases serum adiponectin levels with the improvement of endothelial dysfunction in patients with rheumatoid arthritis (2007)
  • Author(s): Komai N, Morita Y (他3名2番目)
  • Journal Title: Mod Rheumatol 17 Pages: 385-90
  • NAID: 10019778138
  • Peer Reviewed
• [Journal Article] Inhibition of apoptosis-regulated signaling kinase-1 and prevention of congestive heart failure by estrogen (2007)
  • Author(s): Satoh M (他6名1番目)
  • Journal Title: Circulation 115 Pages: 3197-204
  • Peer Reviewed
• [Journal Article] Critical role of endothelial Notch1 signaling in postnatal angiogenesis (2007)
  • Author(s): Takeshita K, Satoh M (他9名2番目)
  • Journal Title: Circ Res 100 Pages: 70-78
  • Peer Reviewed
• [Journal Article] Amelioration of progressive renal injury by genetic manipulation of Klotho gene (2007)
  • Author(s): Haruna Y, Kashihara N, Satoh M (他8名3番目)
  • Journal Title: Proc Natl Acad Sci U S A 104 Pages: 2331-6
  • Peer Reviewed
• [Journal Article] Pioglitazone ameliorates endothelial dysfunction in obese rats with nephropathy (2007)
  • Author(s): Namikoshi T, Satoh M (他6名2番目)
  • Journal Title: Biochem Biophys Res Commun 361 Pages: 835-40
  • Peer Reviewed
• [Journal Article] Olmesartan ameliorates renovascular injury and oxidative stress in Zucker obese rats enhanced by dietary protein (2007)
  • Author(s): Namikoshi T, Tomita N, Satoh M (他5名3番目)
  • Journal Title: Am J Hypertens 20 Pages: 1085-91
  • Peer Reviewed
• [Journal Article] Enhanced TGF-beta/Smad signaling in the early stage of diabetic nephropathy is independent of the AT1a receptor (2007)
  • Author(s): Okazaki Y, Satoh M (他9名3番目)
  • Journal Title: Clin Exp Nephrol 11 Pages: 77-87
  • Peer Reviewed
• [Journal Article] Important role of endogenous hydrogen peroxide in pacing-induced metabolic coronaryvasodilation in dogs in vivo (2007)
  • Author(s): Yada T (他7名1番目)
  • Journal Title: J Am Coll Cardiol 50 Pages: 1272-8
  • Peer Reviewed
• [Journal Article] Changes of asymmetric dimethylarginine, nitric oxide, tetrahydrobiopterin, and oxidative stress in patients with acute myocardial infarction by medical treatments (2007)
  • Author(s): Yada T (他7名1番目)
  • Journal Title: Clin Hemorheol Microcirc 37 Pages: 269-76
  • Peer Reviewed
• [Journal Article] Edaravone preserves coronary microvascular endothelial function after ischemia/reperfusion on the beating canine heart in vivo (2007)
  • Author(s): Sukmawan R, Yada T (他8名2番目)
  • Journal Title: J Pharmacol Sci 104 Pages: 341-8
  • NAID: 10024315221
  • Peer Reviewed
• [Journal Article] Fluvastatin reverses endothelial dysfunction and increased vascular oxidative stress in rat adjuvant-induced arthritis (2007)
  • Author(s): Yoshisuke Haruna
  • Journal Title: Arthritis&Rheumatism 56 Pages: 1827-1835
  • Peer Reviewed
• [Journal Article] Anti-TNF therapy increases serum adiponectin levels with improvement of endothelial dysfunction in patients with rheumatoid arthritis (2007)
  • Author(s): Norio Komai
  • Journal Title: Modern Rheumatology 17 Pages: 385-390
  • Peer Reviewed
• [Presentation] TNFαは血管内皮機能を低下させる-抗サイトカイン療法と心血管保護作用に関連して- (2008)
  • Author(s): 作田建夫(代表:守田吉孝)
  • Organizer: 第19回日本リウマチ学会中国四国支部学術集会
  • Place of Presentation: 広島
  • Year and Date: 2008-10-25
• [Presentation] ラット関節炎モデルの心血管障害 : 酸化ストレス亢進と心筋肥大 (2008)
  • Author(s): 作田建夫(代表:守田吉孝)
  • Organizer: 第36回日本臨床免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-17
• [Presentation] Systemic Inflammation in Rat Arthritis Model Potentiates Hypertensive and Vascular Hypertrophic Responses to Angiotensin II (2008)
  • Author(s): Yoshitaka Morita
  • Organizer: 第13回アジア太平洋リウマチ学会(APLAR)
  • Place of Presentation: 横浜
  • Year and Date: 2008-09-25
• [Presentation] Systemic inflammation in rat arthritis model potentiates hypertensive and vascular hypertrophic responses to angiotensin II (2008)
  • Author(s): 守田吉孝
  • Organizer: 第13回アジア太平洋リウマチ学会(APLAR)
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2008-09-25
• [Presentation] アジュバント関節炎はアンジオテンシンII持続投与高血圧ラットの心機能を低下させる (2008)
  • Author(s): 作田建夫(代表:守田吉孝)
  • Organizer: 第52回日本リウマチ学会総会・学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2008-04-23
• [Presentation] アジュバント関節炎はアンジオテンシンII持続投与高血圧ラットの心機能を低下させる (2008)
  • Author(s): 作田建夫
  • Organizer: 第52回日本リウマチ学会総会・学術集会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2008-04-23
• [Presentation] アンジオテンシンIIによる血管内皮機能障害はアジュバント関節炎の誘導にて増悪する (2008)
  • Author(s): 守田吉孝
  • Organizer: 第52回日本リウマチ学会総会・学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2008-04-22
• [Presentation] アンジオテンシンIIによる血管内皮機能障害はアジュバント関節炎の誘導にて増悪する (2008)
  • Author(s): 守田吉孝
  • Organizer: 第52回日本リウマチ学会総会・学術集会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2008-04-22
• [Presentation] 高血圧性血管内皮障害は関節炎による全身性炎症にて増悪する-動物モデルを用いた検討- (2007)
  • Author(s): 作田建夫(代表:守田吉孝)
  • Organizer: 第18回日本リウマチ学会中国・四国支部学術集会
  • Place of Presentation: 倉敷
  • Year and Date: 2007-10-13
• [Presentation] 高血圧性血管内皮障害は関節炎による全身性炎症にて増悪する一動物モデルを用いた検討 (2007)
  • Author(s): 作田 建夫
  • Organizer: 第18回日本リウマチ学会中国・四国支部学術集会
  • Place of Presentation: 岡山県倉敷市
  • Year and Date: 2007-10-13
• [Presentation] アジュバント関節炎ラットの内皮機能障害と過剰血管酸化ストレスに対するスタチンの効果検討 (2007)
  • Author(s): 守田吉孝
  • Organizer: 第51回日本リウマチ学会総会・学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2007-04-27
• [Presentation] アジュバント関節炎ラットの内皮機能障害と過剰血管酸化ストレスに対するスタチンの効果検討 (2007)
  • Author(s): 守田 吉孝
  • Organizer: 第51回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2007-04-27