Identification and regulation of differentiation In bone marrow -derived vascular progenitor cells

• Project/Area Number: 13557061
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 展開研究
• Research Field: Circulatory organs internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: HIRATA Yasunobu The University or Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (70167609)
• Co-Investigator(Kenkyū-buntansha): SATA Masataka The University or Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (80345214) ; SUZUKI Etsu The University or Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (40313134)
• Project Period (FY): 2001 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥11,600,000 (Direct Cost: ¥11,600,000); Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2001: ¥9,000,000 (Direct Cost: ¥9,000,000)
• Keywords: neointima / arteriosclerosis / stem cell / bone marrow / VSMC / LacZ / 成体幹細胞 / 新生内膜I / 欠陥平滑筋 / LacZ

Research Abstract

We have suggested that bone marrow-derived progenitor cells may contribute to the pathogenesis of vascular diseases. On the other hand, It was reported that bone marrow cells do not participate substantially in vascular remodeling in other experimental systems. in this study, three distinct types of mechanical vascular injuries were induced in the same mouse whose bone marrow had been reconstituted with that of GFP or LacZ mice. All injuries are known to cause smooth muscle cell (SMC) hyperplasia. At 4 weeks after wire-mediated endovascular injury, a significant number of the neointlmal and medial cells derived from bone marrow. In contrast, marker-positive cells were seldom detected in the lesion induced by perivascular cuff replacement. There were only a few bone marrow-derived cells in the neointima after ligation of the common carotid artery. These results indicate that the origin of Intimal cells is diverse and that contribution of bone marrow-derived cells to neointlmal hyperpiasia depends on the type of model.

Research Products

• [Publications] Sata M, Sugawara S, Yoshizumi M, Ouchi Y, Hirata Y, Nagai R: "Acute and chronic smooth muscle ell apoptosis after mechanical vascular injury can occur independently of the fas-death pathway."Arterioscler Thromb Vasc Biol. 21. 1733-1737 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nishimatsu H, Hirata Y 他: "Role of endogenous adrenomedullin in the regulation of vascular tone and ischemic renal injury : studies on transgenic/knockout mice of adrenomedullin gene."Circ Res. 90. 657-663 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sata M, Hirata Y 他: "Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis."Nat Med. 29. 403-409 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Suzuki E, Nishimatsu H, Satonaka H, Walsh K, Goto A, Omata M, Fujita T, Nagai R, Hiiata Y: "Angiotensin II induces myocyte enhances factor 2- and calcineurin/ nuclear factor of activated T cell-dependent transcriptional activation in vascular myocytes."Circ Res. 90. 1004-1011 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shindo T, Manabe I, Maemura K, Sata M, Hirata Y, Kadowaki T, Nagai R, etc.: "Kruppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling."Nat Med. 8. 856-863 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Abe M, Sata M, Nishimatsu H, Nagata D, Suzuki E, Terauchi Y, Kadowaki T, Matsuo H, Hirata Y, Nagai R: "Adrenomedullin augments collateral development in response to acute ischemia."Biochem Biophys Res Commun. 306. 10-15 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sata M, Tanaha K, Ishizaha N, Hirata Y, Nagai R: "Absence of p53 leads to accelerated neointimal hyperplasia after vascuhir injury."Arterioscler Thromb Vase Biol. 23. 1548-1552 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tnaka K, Hirata Y 他: "Diverse contribution of bone marrow cells to neointimal hyperplasia after mechanical vascular injuries."Clrc Res. 93. 783-790 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Satonaka H, Hirata Y 他: "Calcineurin promotes the expression of monocyte chemoattractant protein-1 in vascular myocytes and mediates vascular inflammation."Circ Res. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Niu P, Hirata Y 他: "Protective Effects of Endogenous Adrenomedullin on Cardiac Hypertrophy, Fibrosis, and Renal Damage."Circulation. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sata M, Sugiura S, Yoshlzumi M, Ouchi Y, Hirata Y, Nagal R: "Acute and chronic smooth muscle cell apoptosls after mechanical vascular injury can occur independently of the fas-death pathway."Arterioscier Thromb Vasc Biol. 21. 1733-1737 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nishimatsu H, Hirata Y, Shindo T, Kurihara H, Kakoki M, Nagata D, Hayakawa H, Satonaka H, Sata M, Tojo A, Suzuki E, Kangawa K, Matsuo H, Kitamura T, Nagai R: "Role of endogenous adrenomedullin in the regulation of vascular tone and ischemic renal injury : studies on transgenic/knockout mice of adrenomedullin gene."Circ Res. 90. 657-663 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sata M, Saiura A, Kunisato A, Tojo A, Okada S, Tokuhisa T, Hirai H, Mauuchi M, Hirata Y, Nagai R: "Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis."Nat Med. 8. 403-409 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Suzuki E, Nishimatsu H, Satonaka H, Walsh K, Goto A, Omata M, Fujita T, Nagai R, Hirata Y: "Anglotensin II Induces myocyte enhancer factor 2-and calcineurin/nuclear factor of activated T cell-dependent transcriptional activation in vascular myocytes."Circ Res. 90. 1004-1011 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Shindo T, Manabe I, Fukushima Y, Tobe K, Aizawa K, Miyamoto S.Kawai-Kowase K, Moriyama N, Imai Y, Kawakami H, Nishimatsu H, Ishikawa T, Suzuki T, Morita H, Maemura K, Sota M, Hirata Y, Komukai M, Kagechika H, Kadowaki T, Kuraboyashi M, Nagai R: "Kruppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling."Nat Med. 8. 856-863 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Abe M, Sata M, Nishimatsu H, Nagata D, Suzuki E, Terauchi Y, Kadowaki T, Minamino N, Kangawa K, Matsuo H, Hirata Y, Nagai R: "Adrenomedullin augments collateral development in response to acute ischemia.."Biochem Biophys Res Commun. 306. 10-15 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sata M, Tanaka K, Ishizaka N, Hirata Y, Nagai R: "Absence of p53 leads to accelerated neointimal hyperplasia after vascular injury."arterioscler Thromb Vasc Biol. 23. 1548-1552 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tnaka K, Sata M, Hirata Y, Nagai R: "Diverse contribution of bone morrow cells to neointimd hyperplasia after mechanical vascular injuries."Circ Res. 93. 783-790 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Satonaka H, Suzuki E, Nishimatsu H, Takeda R, Goto A, Fujita T, Nagai R, Hirata Y: "Calcineurin promote the expression of monocyte chemoattractant protein-1 in vascular myocytestes and mediates vascular inflammation."Circ Res. (In press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Niu P.Shindo T, Iwata H, limuro S, Tckeda N, Zhang Y, Ebihara A, Suematsu Y, Kangawa K, Hirata Y, Nagai R: "Protective Effects of Endogenous Adrenomedullin on Cardiac Hypertrophy, Fibrosis, and Renal Damage."Circulation. (In press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Satonaka H, Hirata Y 他: "Calcineurin promotes the expression of monocyte chemoattractant protein-1 in vascular myocytes and mediates vascular inflammation."Circ Res. (in press). (2004)
• [Publications] Tanaka K, Hirata Y 他: "Diverse contribution of bone marrow cells to neointimal hyperplasia after mechanical vascular injuries."Circ Res. 93. 783-790 (2003)
• [Publications] Sata, M, Hirata, Y 他: "A bsence of p53 leads to accelerated neointimal hyperplasia after vascular injury."Arterioscier.Thromb.Vasc.Biol. 23. 1548-0552 (2003)
• [Publications] Nishimatsu H, Hirata Y 他: "Endothelial responses of the aorta from adrenomedullin transgenic mice and knockout mice."Hypertens Res. 26 Suppl. S79-S84 (2003)
• [Publications] Abe M, Hirata Y 他: "Adrenomedullin augments collateral development in response to acute ischemia."Biochem Biophys Res Commun. 306. 10-15 (2003)
• [Publications] Fukino K, Hirata Y 他: "Genetic background influences therapeutic effectiveness of VEGF."Biochem Biophys Res Commun. 310. 143-147 (2003)
• [Publications] Sata M, Hirata Y. et al.: "Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis"Nature Med.. 8. 403-409 (2002)
• [Publications] Suzuki E, Hirata Y. et al.: "Angiotensin II induces myocyte enhancer factor 2-and calcineurin/nuclear factor of activated T cell-dependent transcriptional activation in vascular myocytes"Circ.Res.. 90. 1004-1011 (2002)
• [Publications] Nishimatsu H, Hirata Y. et al.: "Role of endogenous adrenomedullin in the regulation of vascular tone and ischemic renal injury : studies on transgenic/knockout mice of adrenomedullin gene"Circ.Res.. 90. 657-663 (2002)
• [Publications] Shindo T, Hirata Y. et al.: "Kruppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling"Nature Med.. 8. 856-863 (2002)
• [Publications] Sata M, Hirata Y. et al.: "Mouse genetic evidence that tranilast reduces smooth muscle cell hyperplasia via a p21(WAF1)-dependent pathway"Arterioscler Thromb Vasc. Biol.. 22. 1305-1309 (2002)
• [Publications] Suzuki N, Hirata Y. et al.: "Orthogonality of calcium concentration and ability of 4,5-diaminofluorescein (DAF-2) to detect NO"J.Biol.Chem.. 277. 47-49 (2002)
• [Publications] Nagata D, Hirata Y, et al.: "Transcriptional activation of the cyclin D1 gene is mediated by multiple cis elements including SP1 sites and a cyclic AMP responsive element in vascular endothelial cells"J Biol Chem. 276. 662-669 (2001)
• [Publications] Wang Y, Hirata Y, et al.: "Crucial Role of Type 1, but Not Type 3, Inositol 1, 4, 5-Trisphosphate(IP3)Receptors in IP3-Induced Ca2+ Release, Capacitative Ca2+ Entry, and Proliferation of A7r5 Vascular Smooth Muscle Cells"Circ Res. 88. 202-209 (2001)
• [Publications] Kojima H, Hirata Y, et al.: "Bioimaging of nitric oxide with fluorescent indicators based on rhodamine chromophore"Anal Chem. 73. 1967-1973 (2001)
• [Publications] Saiura A, Hirata Y, et al.: "Circulating smooth muscle progenitor cells contribute to atherosclerosis"Nature Med. 7. 382-383 (2001)
• [Publications] Sata M, Hirata Y, et al.: "Acute and chronic smooth muscle cell apoptosis after mechanical vascular injury can occur independently of the fas-death pahtway"Arterioscler Thromb Vasc Biol. 21. 1733-1737 (2001)
• [Publications] Saiura A, Hirata Y, et al.: "Tranilast inhibits transplant-associated coronary arteriosclerosis in a murine model of cardiac transplantation"Eur J Pharmacol. 433. 163-168 (2001)