The functional role of thrombin cleaved osteopontin for the pathogenesis of atherosclerosis

• Project/Area Number: 22790382
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Ehime University
• Principal Investigator: KURATA Mie 愛媛大学, 大学院・医学系研究科, 講師 (80423440)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 炎症 / 粥状動脈硬化 / オステオポンチン / トロンビン切断型オステオポンチン / 動脈硬化 / 慢性炎症 / 血管新生 / 幹細胞 / トロンビン切断型オステオポンチ

Research Abstract

Osteopontin(OPN) which produced in atherosclerotic lesions is cleaved by activated thrombin. We clarified that prevalence of trOPN around intra-plaque vessels which is characterized CD34, recognized as one of the stem cell markers, positive luminal structures. Furthermore, we confirmed that after the mechanical damage of an unstable atherosclerotic plaque increased plasma levels of trOPN. In vitro study, GST-fused recombinant trOPN induced various inflammatory cytokines stronger than fOPN, from mouse resident peritoneal macrophages in a dose dependent manner. These findings suggested that trOPN has a potential not only to be a novel biomarker that reflects the atherothrombotic status in ischemic stroke, but also to be a therapeutic target to suppress the inflammation.

Research Products

• [Journal Article] Plasma thrombin-cleaved osteopontin elevation after carotid artery stenting in symptomatic ischemic stroke patients (2012)
  • Author(s): Kurata M, Okura T, Kumon Y, Tagawa M, Watanabe H, Nakahara T, Tatsuhiko M, Higaki J, Nose M
  • Journal Title: Hypertens Res Volume: 2巻 Pages: 207-212
  • NAID: 10030643794
  • Peer Reviewed
• [Journal Article] Plasma thrombin-cleaved osteopontin elevation after carotid artery stenting in symptomatic ischemic stroke patients. (2012)
  • Author(s): Kurata M, Okura T, Kumon Y, Tagawa M, Watanabe H, Nakahara T, Miyazaki T, Higaki J, Nose M.
  • Journal Title: Hypertens Res. Volume: 35(2) Issue: 2 Pages: 207-212
  • DOI: 10.1038/hr.2011.177
  • NAID: 10030643794
  • Peer Reviewed
• [Journal Article] Osteopontin deficiency protects against aldosterone-induced inflammation, oxidative stress, and interstitial fibrosis in the kidney (2011)
  • Author(s): Irita J, Okura T, Jotoku M, Nagao T, Enomoto D, Kurata M, Desilva VR, Miyoshi K, Matsui Y, Uede T, Denhardt DT, Rittiling SR, Higaki J
  • Journal Title: American Journal of Physiology. Renal Physiology Volume: 301
  • Peer Reviewed
• [Journal Article] Angiotensin II receptor blockade with valsartan decreases plasma osteopontin levels in patients with essential hypertension (2011)
  • Author(s): Kurata M, Okura T, Irita J, Enomoto D, Nagao T, Jotoku M, Miyoshi K, Desilva VR, Higaki J
  • Journal Title: J Hum Hypert Volume: 25巻 Pages: 334-339
  • Peer Reviewed
• [Journal Article] Osteopontin deficiency protects against aldosterone-induced inflammation, oxidative stress, and interstitial fibrosis in the kidney (2011)
  • Author(s): Irita J, Okura T, Kurata M, et al
  • Journal Title: Am J Physiol Renal Physiol Volume: 4
  • Peer Reviewed
• [Journal Article] Angiotensin II receptor blockade with valsartan decreases plasma osteopontin levels in patients with essential hypertension. (2010)
  • Author(s): Kurata M, Okura T, Irita J, et al.
  • Journal Title: J Hum Hypertens. Volume: (e-pub ahead print)
  • Peer Reviewed
• [Presentation] Vulnerable Plaque in Atherosclerosis is Characterized by Microvasculature Involving the Vessels Derived from" Vasa Vasorum Interna" (2012)
  • Author(s): Kurata M, Okura T, Watanabe H, Kumon Y, Tagawa M, Shimazu Y, Aoba T, Nose M, and Higaki J
  • Organizer: The 61th Annual Scientific Session of the American College of Cardiology
  • Place of Presentation: Chicago
• [Presentation] Vulnerable Plaque in Atherosclerosis is Characterized by Microvasculature Involving the Vessels Derived from" Vasa vasorum Intern" (2012)
  • Author(s): Kurata M, Okura T, Watanabe H, Kumon Y, Tagawa M, Shimazu Y, Aoba T, Nose M, and Higaki J
  • Organizer: 第76回日本循環器学会総会
• [Presentation] Vulnerable Plaque in Atherosclerosis is Characterized by Microvasculature Involving the Vessels Derived from "Vasa vasorum Interna" (2012)
  • Author(s): Kurata M, Nose M, Higaki J, et al
  • Organizer: The 61th Annual Scientific Session of the American College of Cardiology
  • Place of Presentation: Chicago USA
• [Presentation] 有症候性脳虚血患者においてトロンビン切断型オステオポンチンは頸動脈ステント留置後に上昇する (2011)
  • Author(s): 倉田美恵、大蔵隆文、入田純、長尾知明、榎本大次郎、檜垣實男
  • Organizer: 第34回日本高血圧学会総会
• [Presentation] Intra-plaque vessel density, inflammatory cells and existence of thrombin-cleaved form of osteopontin are the risk factors for symptomatic stroke (2011)
  • Author(s): Kurata M, Okura T, Watanabe H, Kumon Y, Tagawa M, Higaki J, Nose M
  • Organizer: The 79th European Atherosclerosis Society Congress
  • Place of Presentation: Gothenburg, Sweden
• [Presentation] 有症候性脳虚血患者においてトロンビン切断型オステオポンチンは頸動脈ステント留置後に上昇する (2011)
  • Author(s): 倉田美恵、大蔵隆文、檜垣實男, 他
  • Organizer: 第34回日本高血圧学会総会
  • Place of Presentation: 宇都宮
• [Presentation] Inflammatory cytokine expression in the mouse macrophages responding to thrombin cleaved osteopontin (2010)
  • Author(s): 倉田美恵
  • Organizer: 23rd Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2010-09-28
• [Presentation] Inflammatory Cytokine Expression in the Macrophage Cell Line in Response to Thrombin Cleaved Osteopontin (2010)
  • Author(s): Kurata M, Okura T, Tanaka Y, Miyazaki T, Nagao T, Irita J, Fujino T, Higaki J, and Nose M
  • Organizer: The 23rds Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Vanvouver, Canada