Usefulness of plasma thrombin-cleaved osteopontin (N-half OPN) level on diagnosis of thrombotic disease

• Project/Area Number: 26461112
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Ehime University
• Principal Investigator: Higaki Jitsuo 愛媛大学, 医学系研究科, 教授 (70189744)
• Co-Investigator(Kenkyū-buntansha): 大蔵 隆文 愛媛大学, 医学系研究科, 准教授 (40260385)
• Co-Investigator(Renkei-kenkyūsha): Miyoshi Kenichi 愛媛大学, 大学院医学系研究科, 講師 (50423439) ; Irita Jun 愛媛大学, 医学部附属病院, 講師 (00423442) ; Nagao Tomoaki 愛媛大学, 医学部附属病院, 医員 (20512164)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: オステオポンチン / アテローム血栓性脳梗塞 / thrombin cleaved / osteopontin / 血栓症

Outline of Final Research Achievements

We investigated whether thrombin-cleaved osteopontin (N-half OPN) is useful as a biomarker of acute atherothrombotic stroke. They were divided into the atherothrombotic and non-atherothrombotic groups. N-half OPN, MMP-9 were measured at admission. After excluding patients who met the exclusion criteria, 60 of the 100 patients enrolled in this study. The ischemic stroke subtypes were atherothrombotic (n=28.4%), cardioembolic (n=19.3%) and lacunar (n=13.2%). N-half OPN and MMP-9 levels were significantly higher in the atherothrombotic than in the non-atherothrombotic group. After adjustment for the prevalence of hypertension, diabetes and dyslipidemia, N-half OPN levels of 5.47 pmol/l and MMP-9 levels of >605.5 ng/ml were identified as independent predictors of atherothrombosis. Within 3 hours from stroke onset, only N-half OPN independently predicted atherothrombotic stroke, suggesting usefulness of N-half OPN for diagnosis of the early evaluation of ischemic stroke.

Research Products

• [Journal Article] Plasma thrombin-cleaved osteopontin as a potential biomarker of acute atherothrombotic ischemic stroke (2017)
  • Author(s): Ozaki S, Kurata M, Kumin Y, Matsumoto S, Tagawa M, Watanabe H, Hue S, Higaki J, Ohnishi T
  • Journal Title: Hypertension Research Volume: 40 Pages: 61-66
  • Peer Reviewed
• [Journal Article] Compensatory increase of left atrial external work to left ventricular dysfunction caused by afterload increase (2015)
  • Author(s): Inoue K, Asanuma T, Masuda K, Sakurai D, Higaki J, Nakatani S
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 308 Issue: 3 Pages: 4600-4614
  • DOI: 10.3390/ijms16034600
  • Peer Reviewed / Open Access
• [Journal Article] Carotid hemodynamics is associated with monocyte count determined by serum homocysteine level in patients with essential hypertension (2015)
  • Author(s): Jotoku M, Okura T, Miyoshi KI, Irita J, Nagao T, Kukida M, Tanino A, Kudo K, Enomoto D, Pei Z, Higaki J
  • Journal Title: Clin Exp Hypertens Volume: 1 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Combination therapy with sivelestat and recombinant human soluble thrombomodulin for ARDS and DIC patients (2014)
  • Author(s): Miyoshi S, Ito R, Katayama H, Dote K, Aibiki M, Hamada H, Okura T, Higaki J.
  • Journal Title: Drug Des Devel Ther Volume: 8 Pages: 1211-1219
  • DOI: 10.2147/dddt.s68030
  • Peer Reviewed
• [Journal Article] Hyperhomocysteinemia is one of the risk factors associated with cerebrovascular stiffness in hypertensive patients, especially elderly males (2014)
  • Author(s): Okura T, Miyoshi K, Irita J, Enomoto D, Nagao T, Kukida M, Tanino A, Kudo K, Pei Z, Higaki J
  • Journal Title: Sci Rep Volume: 53 Issue: 1 Pages: 1-5
  • DOI: 10.1038/srep05663
  • Peer Reviewed / Open Access
• [Presentation] Diagnostic Accuracy of ATPstress Dynamic CT Perfusion Imaging as Compared with MR Perfusion Imaging for the Assessment of Myocardial Ischemia (2015)
  • Author(s): Teruyoshi Uetani, Tamami Kouno, Rie Ueno, Hiroshi Kawakami, Akira Fujii, Takayuki Nagai, Kazuhisa Nishimura, Katsuji Inoue, Jun Suzuki, Akiyoshi Ogimoto, Teruhiko Kido, Teruhito Mochizuki, Takafumi Okura, Jitsuo Higaki
  • Organizer: 日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] Different Behavior of Left Atrial Function to Left Ventricular Anterior (2015)
  • Author(s): Ｋａｔｓｕｊｉ Ｉｎｏｕｅ， Ｔｏｓｈｉｈｉｋｏ Ａｓａｍｕｒａ， Ｋａｓｕｍｉ Ｍａｓｕｄａ， Ｄａｉｓｕｋｅ Ｓａｋｕｒａｉ， Ｊｉｔｓｕｏ Ｈｉｇａｋｉ， Ｓａｔｏｓｈｉ Ｎａｋａｔａｎｉ
  • Organizer: 日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] Impact of Serum Eicosapentaenoic AcidArachidonic Acid Ratio for Fatal (2015)
  • Author(s): Kazuhisa Nishimura, Hiroshi Kawakami, Tamami Kouno, Akira Fujii, Teruyoshi Uetani, Takayuki Nagai, Katsuji Inoue, Jun Suzuki, Akiyoshi Ogimoto, Takafumi Okura, Jitsuo Higaki.
  • Organizer: 日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] Evaluation of Portable Monitoring of Sleep Disordered Breathing to (2015)
  • Author(s): Hiroshi Kawakami, Takayuki Nagai, Hirohiko Nakagawa, Rie Ueno, Chiharuko Iio, Kaori Fujimoto, Tamami Kouno, Teruyoshi Uetani, Kazuhisa Nishimura, Tamami Kouno, Katsuji Inoue, Jun Suzuki, Akiyoshi Ogimoto, Tasunori Oka, Takafumi Okura, Jitsuo Higaki.
  • Organizer: 日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] Diagnostic Potential of ATP stress Myocardial CT Perfusion Imaging for Hemodynamically Significant Stenosis: A Comparison with Fractional Flow Reserve (2015)
  • Author(s): Teruyoshi Uetani, Tamami Kouno, Rie Ueno, Hiroshi Kawakami, Akira Fujii, Takayuki Nagai, Kazuhisa Nishimura, Katsuji Inoue, Jun Suzuki, Akiyoshi Ogimoto, Teruhiko Kido, Teruhito Mochizuki, Takafumi Okura, Jitsuo Higaki
  • Organizer: 日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26