Impaired Angiogenesis During Hindlimb Ischemia in Skeletal Muscle-Specific STAT3 Deficient Mice

• Project/Area Number: 24791397
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Kurume University
• Principal Investigator: OHSHIMA Hideki 久留米大学, 医学部, 助教 (90569419)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 下肢虚血 / 血管新生 / サイトカイン / Jak-STAT

Research Abstract

Although the STAT3 activating cytokines play an important role in angiogenesis, little is known about the STAT3 role in skeletal muscle during ischemia-induced angiogenesis. STAT3 was promptly phosphorylated within skeletal muscle, and STAT3-activating cytokine including interleukin-6 and G-CSF were increased during hindlimb ischemia (HLI). Blood-flow recovery after HLI was impaired in skeletal muscle-specific, STAT3 knockout mice (sm-STAT3-KO). The number of CD31 positive cells after HLI was significantly less in sm-STAT3-KO than that in wild-type mice. Real-time PCR array analysis for angiogenesis revealed that the expression levels of angiogenic chemokines and inflammatory cytokines were significantly much lower in sm-STAT3-KO than those in wild-type mice after HLI. These results suggested that angiogenesis during ischemia was impaired in sm-STAT3-KO, possibly through the inhibition of angiogenic chemokines and inflammatory cytokines expression.

Research Products

• [Journal Article] Screening for Fabry disease in patients with left ventricular hypertrophy (2013)
  • Author(s): Mawatari K, Yasukawa H, Oba T, Nagata T, Togawa T, Tsukimura T, Kyogoku S, Ohshima H, Minami T, Sakubaba H, Imaizumi T
  • Journal Title: Int J Cardiol Volume: 167 Pages: 1059-1061
  • Peer Reviewed
• [Journal Article] Screening for Fabry disease in patients with left ventricular hypertrophy (2013)
  • Author(s): Mawatari K, Yasukawa H, Oba T, Nagata T, Togawa T, Tsukimura T, Kyogoku S, Ohshima H, Minami T, Sakuraba H, Imaizumi T
  • Journal Title: Int J Cardiol Volume: 3 Pages: 1959-1961
  • Peer Reviewed
• [Journal Article] Screening for Fabry disease in patients with left ventricular hypertrophy. (2013)
  • Author(s): Mawatari K, Yasukawa H, Oba T, Nagata T, Togawa T, Tsukimura T, Kyogoku S, Ohshima H, Minami T, Sugi Y, Sakuraba H, Imaizumi T.
  • Journal Title: Int J Cardiol Volume: 167 Issue: 3 Pages: 1059-1061
  • DOI: 10.1016/j.ijcard.2012.10.076
  • 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, Yasukawa H, Hoshijima M, Sasaki KI, Futamata N, Fukui D, Mawatari K, Nagata T, Kyogoku S, Ohshima H, Minami T, Nakamura K, Kang D, Yajima T, Knowlton KU, Imaizumi T
  • Journal Title: J Am Coll Cardiol Volume: 59 Pages: 838-852
  • Peer Reviewed
• [Journal Article] Cardiomyocyte-specific transgenic expression of lysyl oxidase-like protein-1 induces cardiac hypertrophy in mice (2012)
  • Author(s): Ohmura H, Yasukawa H, Minami T, Sugi Y, Oba T, Nagata T, Kyougoku S, Ohshima H, Aoki H, Imaizumi T
  • Journal Title: Hypertens Res Volume: 35 Pages: 1063-1068
  • 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, Yasukawa H, Hoshijima M, Sasaki KI, Futamata N, Fukui D, Mawatari K, Nagata T, Kyogoku, S, Ohshima H, Minami T, Nakamura K, Kang D, Yajima T, Knowlton KU, Imaizumi T
  • Journal Title: J Am Coll Cardiol Volume: 59 Pages: 838-852
  • Peer Reviewed
• [Journal Article] Cardiomyocyte-specific transgenic expression of lysyl oxidase-like protein-1 induces cardiac hypertrophy in mice. (2012)
  • Author(s): Ohmura H, Yasukawa H, Minami T, Sugi Y, Oba T, Nagata T, Kyougoku S, Ohshima H, Aoki H, Imaizumi T
  • Journal Title: Hypertens Res Volume: 35 Pages: 1063-1068
  • Peer Reviewed
• [Presentation] Screening for Fabry Disease in Patients with Left Ventricular Hypertrophy (2013)
  • Author(s): Mawatari K, Yasukawa H, Oba T, Nagata T, Kyogoku S, Ohshima H, Minami T, Sugi Y, Imaizumi T
  • Organizer: 第17回日本心不全学会学術集会
  • Place of Presentation: 埼玉
• [Presentation] Cardiac-Specific Deletion of Suppressor of Cytokine Signaling-3 Prevents Doxorubicin-Induced Cardiomyopathy in Mice.The American Heart Association (2012)
  • Author(s): Kyogoku S, Yasukawa H, Nagata T, Oba T, Ohshima H, Minami T, Yajima T, Hoshijima M, Aoki H, Knowlton KU, Imaizumi T
  • Organizer: The 85th Scientific Sessions
  • Place of Presentation: Los Angels, USA
• [Presentation] Pioglitazone Decreases Plasma Fibroblast Growth Factor-21 Levels in Patients with Type 2 Diabetes. The American Heart Association (2012)
  • Author(s): Mawatari K, Tahara N, Yasukawa H, Oba T, Nagata T, Kyougoku S, Ohshima H, Minami T, Mizoguchi M, Sugi Y, Adachi H, Imaizumi T
  • Organizer: The 85th Scientific Sessions
  • Place of Presentation: Los Angels, USA
• [Presentation] Prevention of Doxorubicin-Induced Cardiomyopathy in Cardiac-Specific SOCS3 Deficient Mice by Preserving Energy Metabolism (2012)
  • Author(s): Kyogoku S, Yasukawa H, Nagata T, Oba T, Ohshima H, Minami T, Fukui D, Sugi Y, Aoki H, Imaizumi T
  • Organizer: 第29回 国際心臓研究学会(ISHR)日本部会総会
  • Place of Presentation: 福岡
• [Presentation] Impaired Angiogenesis During Hindlimb Ischemia in Skeletal Muscle-Specific STAT3 Deficient Mice (2012)
  • Author(s): Ohshima H, Yasukawa H, Nagata T, Kyogoku S, Oba T, Mawatari K, Futamata N, Minami T, Sugi Y, Sasaki K, Imaizumi T
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] Prevention of Left Ventricular Remodeling after Acute Myocardial Infarction in Interleukin-17 Deficient Mice (2012)
  • Author(s): Minami T, Yasukawa H, Nagata T, Oba T, Kyogoku S, Ohshima H, Aoki H, Yoshimura A, Imaizumi T
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] Pioglitazone Decreases Plasma Fibroblast Growth Factor-21 Levels in Patients with Type 2 Diabetes (2012)
  • Author(s): 馬渡一寿, 田原宣広, 安川秀雄, 大場豊治, 二又誠義, 永田隆信, 京極幸子, 大島英樹, 南知子, 溝口ミノリ, 足達寿, 今泉勉
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
• [Presentation] Cardiac-Specific Deletion of Suppressor of Cytokine Signaling-3 Prevents Doxorubicin-Induced Cardiomyopathy in Mice. (2012)
  • Author(s): Kyogoku S, Yasukawa H, Nagata T, Oba T, Ohshima H, Minami T, Yajima T, Hoshijima M, Aoki H, Knowlton KU, Imaizumi T
  • Organizer: The American Heart Association, The 85th Scientific Sessions
  • Place of Presentation: Los Angels, USA
• [Presentation] Pioglitazone Decreases Plasma Fibroblast Growth Factor-21 Levels in Patients with Type 2 Diabetes. (2012)
  • Author(s): Mawatari K, Tahara N, Yasukawa H, Oba T, Nagata T, Kyougoku S, Ohshima H, Minami T, Mizoguchi M, Sugi Y, Adachi H, Imaizumi T
  • Organizer: The American Heart Association, The 85th Scientific Sessions
  • Place of Presentation: Los Angels, USA
• [Presentation] Prevention of Doxorubicin-Induced Cardiomyopathy in Cardiac-Specific SOCS3 Deficient Mice by Preserving Energy Metabolism. (2012)
  • Author(s): Kyogoku S, Yasukawa H, Nagata T, Oba T, Ohshima H, Minami T, Fukui D, Sugi Y, Aoki H, Imaizumi T
  • Organizer: 第29回 国際心臓研究学会（ISHR）日本部会総会
  • Place of Presentation: 福岡
• [Presentation] Prevention of Doxorubicin-Induced Cardiomyopathy in Cardiac-Specific SOCS3 Deficient Mice by Augmenting STAT3 Signaling Pathway. (2012)
  • Author(s): 京極幸子、安川秀雄 、永田隆信 、大場豊治 、大島英樹 、南 知子、福井大介 、 杉 雄介 、青木浩樹 、今泉勉
  • Organizer: 第35回 心筋代謝研究会
  • Place of Presentation: 東京
• [Remarks]
  • URL: http://www.kurume-shinzo.com
• [Remarks]
  • URL: http://www.med.kurume-u.ac.jp/med/kucri/
• [Remarks] 久留米大学医学部心臓・血管内科
  • URL: http://www.kurume-shinzo.com