Translational research for new drug development by exploration of the involvement of hematopoietic stem cells in vascular remodeling and atherogenesis

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18590986
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kyoto University
• Principal Investigator: YOKODE Masayuki Kyoto University, GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF CLINICAL INNOVATIVE MEDICINE, PROFESSOR (20252447)
• Co-Investigator(Kenkyū-buntansha): ARAI Hidenori KYOTO UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF GERIATRIC MEDICINE, ASSOCIATE PROFESSOR (60232021) ; MURAYAMA Toshinori KYOTO UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF CLINICAL INNOVATIVE MEDICINE, ASSISTANT PROFESSOR (30378765)
• Project Period (FY): 2006 – 2007
• Keywords: ATHEROSCLEROSIS / STEM CELLS / ANGIOGENESIS / TRANSCRIPTION FACTOR / MORPHOGENESIS / THROMBOXANE / PROSTACYCLIN / REMODELING

Research Abstract

During the research period, the researchers tried to explore the molecular and cellular mechanism for the involvement of bone marrow (BM)-derived stem cells in vascular remodeling and atherogenesis. For this purpose, the researchers applied a polyethylene cuff on to the mouse femoral artery to observe the process of vascular remodeling. By this experimental model, the researchers were able to show that the protection of atherogenesis in thromboxinane (TP)(-/-) mice is not associated with TP in BM-derived cells and that BM-derived cells can contribute to the development of atherosclerosis in the presence of hypercholesterolemia. The researchers also disclosed that mulberry leaf aqueous fractions inhibit atherogenesis both in vivo and in vitro.

Research Products

• [Journal Article] Swimming reduced the severity of atherosclerosis in apolipoprotein Edeficient mice by antioxidant effects (2007)
  • Author(s): Okabe T, Shimada K, Hattori M Murayama T, Yokode M, Kita T, Kishimoto C
  • Journal Title: Cardiovasc Res 74 Pages: 537-545
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] A Higeh Glycolytic Flux Supports the Proliferative Potential of Murine Embryonic Stem Cells (2007)
  • Author(s): Kondoh H, Llenart ME, Nakashima Y, Yokode M, Tanaka M, Bernard D, Gil J, Beach D
  • Journal Title: Antioxid Redox Signal 9 Pages: 293-299
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] SRY-Related HMG Box 9 Regulated the expression of Col4a2 through Transactivating Its enhancer Element in Mesangial Cells (2007)
  • Author(s): Sumi E, Iehara N, Akiyama H, Matsubara T, Mima A, Kanemori H, Fukatsu A, Salant DJ, Kita T, Arai H, Doi T
  • Journal Title: Am J Pathol 170 Pages: 1854-1864
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. (2007)
  • Author(s): Losordo DW, Schatz RA, White CJ, Udelson JE, Veereshwarayya V, Durgin M, Poh KK, Weinstein R, Kearney M, Chaudhry M, Burg A, Eaton L, Heyd L, Thorne T, Shturman L, Hoffmeister P, Story K, Zak V, Dowling D, Traverse JH, Olson RE, Flanagan J, Sodano D, Murayama T, Kawamoto A, Kusano KF, Wollins J, Welt F, Shah P, Soukas P, Asahara T, Henry TD
  • Journal Title: Circulation 115 Pages: 3165-3172
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Mulberry leaf powder prevents atherosclerosis in apolipoprotein E-deficient mice. (2007)
  • Author(s): Harauma A, Murayama T, Ikeyama K, Sano H, Arai H, Takano R, Kita T, Hara S, Kamei K, Yokode M
  • Journal Title: Biochem Biophys Res Commun 358 Pages: 751-756
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Mulberry leaf aqueous fractions inhibit TNF-alpha-induced nuclear factor kappaB(NF-kappaB)activation and lectin-like oxidized LDL receptor-1(LOX-1)expression in vascular endothelial cells. (2007)
  • Author(s): Shibata Y, Kume N, Arai H, Hayashida K, Inui-Hayashida A, Minami M, Mukai E, Toyohara M, Harauma A, Murayama T, Kita T, Hara S, Kamei K, Yokode M
  • Journal Title: Atherosclerosis 193 Pages: 751-756
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Hypercholesterolemia contributes to the development of atherosclerosis and vascular remodeling by recruiting bone marrow-derived cells in cuff-induced vascular injury. (2007)
  • Author(s): Xu Y, Arai H, Murayama T, Kita T, Yokode M
  • Journal Title: Biochem Biophys Res Commun 363 Pages: 782-787
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Exercise training reduces severity of atherosclerosis in apolipoprotein Eknockout mice via nitric oxide. (2007)
  • Author(s): Shimada K, Kishimoto C, Okabe TA, Hattori M, Murayama T, Yokode M, Kita T
  • Journal Title: Circ J 71 Pages: 1147-1151
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Inhibition of MCP-1/CCR2 pathway ameliorates the development of diabetic nephropathy. (2007)
  • Author(s): Kanamori H, Matsubara T, Mima A, Sumi E, Nagai K, Takahashi T, Abe H, Iehara N, Fukatsu A, Okamoto H, Kita T, Doi T, Arai H.
  • Journal Title: Biochem Biophys Res Commun 360 Pages: 772-777
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Gender Difference In ICER Iγ Transgenic Diabetic Mouse. (2007)
  • Author(s): Inada A, Arai H, Nagai K, Miyazaki J, Nomura K, Kanamori H, Yamada Y, Akashi K, Weir GC, Seino Y, Fukatsu A
  • Journal Title: Bioscience, Biotechnology, and Biochemistry 71 Pages: 1920-1926
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Roles of coagulation pathway and factor Xa in rat mesangioproliferative glomerulonephritis. (2007)
  • Author(s): Nomura K, Liu N, Nagai K, Hasegawa T, Kobayashi I, Nogaki F, Tanaka M, Arai H, Fukatsu A, Kita T, Ono T
  • Journal Title: Lab Invent 87 Pages: 150-160
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Swimming reduced the severity of atherosclerosis in apolipoprotein E deficient mice by antioxidant effects (2007)
  • Author(s): Okabe, T., Shimada, K., Hattori, M., Muravama, T., Yokode, M., Kita, T., Kishimoto, C
  • Journal Title: Cardiovasc Res Vol. 74(Peer reviewed) Pages: 537-545
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A High Glycolytic Flux Supports the Proliferative Potential of Murine Embryonic Stem Cells (2007)
  • Author(s): Kondoh, H., Llenart, ME., Nakashima, Y., Yokode, M., Tanaka, M., Bernard, D., Gil, J., Beach, D
  • Journal Title: Antioxid Redox Signal Vol. 9(Peer reviewed) Pages: 293-299
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] SRY-Related HMG Box 9 Regulated the expression of Co14a2 through Transactivating Its enhancer Element in Mesangial Cells (2007)
  • Author(s): Sumi, E., Iehara, N., Akiyama, H., Matsubara, T., Mima, A., Kanemori, H., Fukatsu, A., Salant, DJ., Kita, T., Arai, H., Doi, T
  • Journal Title: Am J Pathol Vol. 170(Peer reviewed) Pages: 1854-1864
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Intramyocardial transplantation of autologous CD34 + stem cells for intractable angina : a phase Ill double-blind, randomized controlled trial (2007)
  • Author(s): Losordo, DW., Schatz, RA., White, CJ., Udelson, JE., Veereshwarayya, V., Durgin, M., Poh, KK., Weinstein, R., Kearney, M., Chaudhry, M., Burg, A., Eaton, L., He, ydL., Thorne, T., Shturman, L., Hoffmeister, P., Story, K., Zak, V., Dowling, D., Traverse, JH., Olson, RE., Flanagan, J., Sodano, D., Muravama, T., Kawamoto, A., Kusano, KF., Wollins, J., Welt, F., Shah, P., Soukas, P., Asahara, T., Henry, TD
  • Journal Title: Circulation Vol. 115(Peer reviewed) Pages: 3165-3172
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mulberry leaf powder prevents atherosclerosis in apolipoprotein E-deficient mice (2007)
  • Author(s): Harauma, A., Muravama, T., Ikeyama, K., Sano, H., Arai, H., Takano, R., Kita, T., Hara, S., Kamei, K., Yokode, M
  • Journal Title: Biochem Biophys Res Commun Vol. 358(Peer reviewed) Pages: 751-756
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mulberry leaf aqueous fractions inhibit TNF-alpha-induced nuclear factor kappaB (NF-kappaB) activation and lectin-like oxidized LDL receptor-1 (LOX-1) expression in vascular endothelial cells (2007)
  • Author(s): Shibata, Y., Kume, N., Arai, H., Hayashida, K., Inui-Hayashida, A., Minami, M., Mukai, E., Toyohara, M., Harauma, A., Muravama, T., Kita, T., Hara, S., Kamei, K., Yokode, M
  • Journal Title: Atherosclerosis Vol. 193(Peer reviewed) Pages: 751-756
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hypercholesterolemia contributes to the development of atherosclerosis and vascular remodeling by recruiting bone marrow-derived cells in cuff-induced vascular injury (2007)
  • Author(s): Xu, Y., Arai, H., Muravama, T., Kita, T., Yokode, M
  • Journal Title: Biochem Biophys Res Commun Vol. 363(Peer reviewed) Pages: 782-787
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Exercise training reduces severity of atherosclerosis in apolipoprotein E knockout mice via nitric oxide (2007)
  • Author(s): Shimada, K., Kishimoto, C., Okabe, TA., Hattori, M., Muravama, T., Yokode, M., Kita, T
  • Journal Title: Circ J Vol. 71(Peer reviewed) Pages: 1147-1151
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of MCP-1/CCR2 pathway ameliorates the development of diabetic nephropathy (2007)
  • Author(s): Kanamori, H., Matsubara, T., Mima, A., Suit, E., Nagai, K., Takahashi, T., Abe, H., Iehara, N., Fukatsu, A., Okamoto, H., Kita, T., Doi, T., Arai, H
  • Journal Title: Biochem Biophys Res Commun Vol. 360(Peer reviewed) Pages: 772-777
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Gender Difference In ICER Ir Transgenic Diabetic Mouse (2007)
  • Author(s): Inada, A., Arai, H., Nagai, K., Miyazaki, J., Nomura, K., Kanamori, H., Yamada, Y., Akashi, K., Weir, GC., Seino, Y., Fukatsu, A
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Vol. 71(Peer reviewed) Pages: 1920-1926
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Roles of coagulation pathway and factor Xa in rat mesangioproliferative glomerulonephritis (2007)
  • Author(s): Nomura, K., Liu, N., Nagai, K., Hasegawa, T., Koba, yashi, I., Nogaki, F., Tanaka, M., Arai, H., Fukatsu, A., Kita, T., Ono, T
  • Journal Title: Lab Invent Vol. 87(Peer reviewed) Pages: 150-160
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Protection of atherogenesis in thromboxane A2 receptor-deficient mice is not assocated with thromboxne A2 receptor in bone marrow-derived cells (2006)
  • Author(s): Zhuge X, Arai H, Xu Y, Murayama T, Kobayashi T, Narumiya S, Kita T, Yokode M
  • Journal Title: Biochemical and Biophysucal Research Communications Vol.11No.4 Pages: 276-279
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Angiotensin II-dependent Src and Smadl signaling pathway is crucial for the development of diabetic nephropathy (2006)
  • Author(s): Mima A, Matsubara T, Arai H, Abe H, Nagai K, Kanamori H, Fukatsu A, Salant DJ, Fukatsu A, Kita T, Doi T
  • Journal Title: Lab Invest Vol.86No.1 Pages: 927-939
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Collaboration between university hospitals and local medical communities in Japan evaluated by a questionnaire among doctors. (2006)
  • Author(s): Tanaka M, Yokode M
  • Journal Title: Geriatr Gerontol Int Vol.6No.4 Pages: 209-215
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Comprehensive Geriatric Assessment for outpatients is important for the detection of functional disabilities and depressive symptoms associated with sensory impairment as well as for the screening of cognitive impairment (2006)
  • Author(s): Sumi E, Takechi H, Wada T, Ishine M, Wakatsuki Y, Murayama T, Yokode M, Tanaka M, Kita T, Matsubayashi K, Arai H
  • Journal Title: Geriatr Gerontol Int Vol.6No.2 Pages: 94-100
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Protection of atherogenesis in thromboxane A2 receptor-deficient mice is not assocated with thromboxne A2 receptor in bone marrow-derived cells (2006)
  • Author(s): Zhuge, X., Arai, H., Xu, Y., Muravama, T., Kobayashi, T., Narumiya, S., Kita, T., Yokode, M
  • Journal Title: Biochemical and Biophysucal Research Communications Vol. 11, No.4(Peer reviewed) Pages: 276-279
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Collaboration between university hospitals and local medical communities in Japan evaluated by a questionnaire among doctors (2006)
  • Author(s): Tanaka, M., Yokode, M
  • Journal Title: Geriatr Gerontol Int Vol. 6, No.4(Peer reviewed) Pages: 209-215
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Comprehensive Geriatric Assessment for outpatients is important for the detection of functional disabilities and depressive symptoms associated with sensory impairment as well as for the screening of cognitive impairment (2006)
  • Author(s): Sumi, E., Takechi, H., Wada, T., Ishine, M., Wakatsuki, Y., Muravama, T., Yokode, M., Tanaka, M., Kita, T., Matsubayashi, K., Arai, H
  • Journal Title: Geriatr Gerontol Int Vol. 6, No.2(Peer reviewed) Pages: 94-100
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Angiotensin ll-dependent Src and Smadl signaling pathway is crucial for the development of diabetic nephropathy (2006)
  • Author(s): Mima, A., Matsubara, T., Arai, H., Abe, H., Nagai, K., Kanamori, H., Fukatsu, A., Salant, DJ., Fukatsu, A., Kita, T., Doi, T
  • Journal Title: Lab Invest Vol. 86, No.1(Peer reviewed) Pages: 927-939
  • Description: 「研究成果報告書概要(欧文)」より