Published online before print December 11, 2003, doi: 10.1161/01.RES.0000111527.42357.62
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on May 19, 2003
Revised on November 21, 2003
Accepted on November 25, 2003
Matrix Metalloproteinase-9 Is Required for Adequate Angiogenic Revascularization of Ischemic Tissues. Potential Role in Capillary Branching
Chad Johnson ;
From the Wallace H. Coulter Department of Biomedical Engineering (C.J., H.-J.S., Z.S.G.), Georgia Institute of Technology/Emory University School of Medicine, Atlanta, Ga; Division of Cardiology (S.M.L., Z.S.G.), Emory School of Medicine, Atlanta, Ga; McKnight Vision Research Center (M.E.F.), Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Fla.
* To whom correspondence should be addressed. E-mail: zgalis{at}emory.edu.
Angiogenesis, an essential component of a variety of physiological and pathological processes, offers attractive opportunities for therapeutic regulation. We hypothesized that matrix metalloproteinase (MMP)-9 genetic deficiency (-/-) will impair angiogenesis triggered by tissue ischemia, induced experimentally by femoral artery ligation in mice. To investigate the role of MMP-9, we performed a series of biochemical and histological analyses, including zymography, simultaneous detection of perfused capillaries, MMP-9 promoter activity, MMP-9 protein, and macrophages in MMP-9-/- and wild-type (WT) mice. We found that ischemia resulted in doubling of capillary density in WT and no change in the MMP-9-/- ischemic tissues, which translated into increased (39%) perfusion capacity only in the WT at 14 days after ligation. We also confirmed that capillaries in the MMP-9-/- presented significantly (P<0.05) less points of capillary intersections, interpreted by as decreased branching. The combined conclusions from simultaneous localizations of MMP-9 expression, capillaries, and macrophages suggested that macrophage MMP-9 participates in capillary branching. Transplantation of WT bone marrow into the MMP-9-/-, restored capillary branching, further supporting the contribution of bone marrow-derived macrophages in supplying the necessary MMP-9. Our study indicates that angiogenesis triggered by tissue ischemia requires MMP-9, which may be involved in capillary branching, a potential novel role for this MMP that could be exploited to control angiogenesis.
Key words: angiography • macrophage • imaging • microvessels • bone-marrow transplantation
This article has been cited by other articles:
 |
|
 |
|
  V. C. Ardi, P. E. Van den Steen, G. Opdenakker, B. Schweighofer, E. I. Deryugina, and J. P. Quigley Neutrophil MMP-9 Proenzyme, Unencumbered by TIMP-1, Undergoes Efficient Activation in Vivo and Catalytically Induces Angiogenesis via a Basic Fibroblast Growth Factor (FGF-2)/FGFR-2 Pathway J. Biol. Chem., September 18, 2009; 284(38): 25854 - 25866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-H. Huang, Y.-H. Chen, C.-H. Wang, J.-S. Chen, H.-Y. Tsai, F.-Y. Lin, W.-Y. Lo, T.-C. Wu, M. Sata, J.-W. Chen, et al. Matrix Metalloproteinase-9 Is Essential for Ischemia-Induced Neovascularization by Modulating Bone Marrow-Derived Endothelial Progenitor Cells Arterioscler Thromb Vasc Biol, August 1, 2009; 29(8): 1179 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Lukkarinen, A. Hogmalm, U. Lappalainen, and K. Bry Matrix Metalloproteinase-9 Deficiency Worsens Lung Injury in a Model of Bronchopulmonary Dysplasia Am. J. Respir. Cell Mol. Biol., July 1, 2009; 41(1): 59 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hughes, A. A. Fu, A. Puggioni, J. F. Glockner, B. Anwer, A. M. McGuire, D. Mukhopadhyay, and S. Misra Adventitial transplantation of blood outgrowth endothelial cells in porcine haemodialysis grafts alleviates hypoxia and decreases neointimal proliferation through a matrix metalloproteinase-9-mediated pathway--a pilot study Nephrol. Dial. Transplant., January 1, 2009; 24(1): 85 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Krady, J. Zeng, J. Yu, S. MacLauchlan, E. A. Skokos, W. Tian, P. Bornstein, W. C. Sessa, and T. R. Kyriakides Thrombospondin-2 Modulates Extracellular Matrix Remodeling during Physiological Angiogenesis Am. J. Pathol., September 1, 2008; 173(3): 879 - 891. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Silvestre, Z. Mallat, A. Tedgui, and B. I. Levy Post-ischaemic neovascularization and inflammation Cardiovasc Res, May 1, 2008; 78(2): 242 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Zayed, W. Yuan, T. M. Leisner, D. Chalothorn, A. W. McFadden, M. D. Schaller, M. E. Hartnett, J. E. Faber, and L. V. Parise CIB1 Regulates Endothelial Cells and Ischemia-Induced Pathological and Adaptive Angiogenesis Circ. Res., November 26, 2007; 101(11): 1185 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Haas, J. L. Doyle, M. R. Distasi, L. E. Norton, K. M. Sheridan, and J. L. Unthank Involvement of MMPs in the outward remodeling of collateral mesenteric arteries Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2429 - H2437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Malik, K. Day, I. Perrault, D.S. Charnock-Jones, and S. K. Smith Reduced levels of VEGF-A and MMP-2 and MMP-9 activity and increased TNF-{alpha} in menstrual endometrium and effluent in women with menorrhagia Hum. Reprod., August 1, 2006; 21(8): 2158 - 2166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. You, L. Waeckel, T. G. Ebrahimian, O. Blanc-Brude, P. Foubert, V. Barateau, M. Duriez, S. LeRicousse-Roussanne, J. Vilar, E. Dejana, et al. Increase in Vascular Permeability and Vasodilation Are Critical for Proangiogenic Effects of Stem Cell Therapy Circulation, July 25, 2006; 114(4): 328 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bergeron and L.-P. Boulet Structural changes in airway diseases: characteristics, mechanisms, consequences, and pharmacologic modulation. Chest, April 1, 2006; 129(4): 1068 - 1087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Janssens and H. R. Lijnen What has been learned about the cardiovascular effects of matrix metalloproteinases from mouse models? Cardiovasc Res, February 15, 2006; 69(3): 585 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Anghelina, P. Krishnan, L. Moldovan, and N. I. Moldovan Monocytes/Macrophages Cooperate with Progenitor Cells during Neovascularization and Tissue Repair: Conversion of Cell Columns into Fibrovascular Bundles Am. J. Pathol., February 1, 2006; 168(2): 529 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Lindsey, G. P. Escobar, L. W. Dobrucki, D. K. Goshorn, S. Bouges, J. T. Mingoia, D. M. McClister Jr., H. Su, J. Gannon, C. MacGillivray, et al. Matrix metalloproteinase-9 gene deletion facilitates angiogenesis after myocardial infarction Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H232 - H239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zijlstra, M. Seandel, T. A. Kupriyanova, J. J. Partridge, M. A. Madsen, E. A. Hahn-Dantona, J. P. Quigley, and E. I. Deryugina Proangiogenic role of neutrophil-like inflammatory heterophils during neovascularization induced by growth factors and human tumor cells Blood, January 1, 2006; 107(1): 317 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Lee, S. Dahi, R. Mahimkar, N. L. Tulloch, M. A. Alfonso-Jaume, D. H. Lovett, and R. Sarkar Intronic regulation of matrix metalloproteinase-2 revealed by in vivo transcriptional analysis in ischemia PNAS, November 8, 2005; 102(45): 16345 - 16350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Gagne, N. Tihonov, X. Li, J. Glaser, J. Qiao, M. Silberstein, H. Yee, E. Gagne, and P. Brooks Temporal Exposure of Cryptic Collagen Epitopes within Ischemic Muscle during Hindlimb Reperfusion Am. J. Pathol., November 1, 2005; 167(5): 1349 - 1359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Heissig, S. Rafii, H. Akiyama, Y. Ohki, Y. Sato, T. Rafael, Z. Zhu, D. J. Hicklin, K. Okumura, H. Ogawa, et al. Low-dose irradiation promotes tissue revascularization through VEGF release from mast cells and MMP-9-mediated progenitor cell mobilization J. Exp. Med., September 19, 2005; 202(6): 739 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yu, E. D. deMuinck, Z. Zhuang, M. Drinane, K. Kauser, G. M. Rubanyi, H. S. Qian, T. Murata, B. Escalante, and W. C. Sessa Endothelial nitric oxide synthase is critical for ischemic remodeling, mural cell recruitment, and blood flow reserve PNAS, August 2, 2005; 102(31): 10999 - 11004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Nikkola, P. Vihinen, M.-S. Vuoristo, P. Kellokumpu-Lehtinen, V.-M. Kahari, and S. Pyrhonen High Serum Levels of Matrix Metalloproteinase-9 and Matrix Metalloproteinase-1 Are Associated with Rapid Progression in Patients with Metastatic Melanoma Clin. Cancer Res., July 15, 2005; 11(14): 5158 - 5166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Hallmann, N. Horn, M. Selg, O. Wendler, F. Pausch, and L. M. Sorokin Expression and Function of Laminins in the Embryonic and Mature Vasculature Physiol Rev, July 1, 2005; 85(3): 979 - 1000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tojo, M. Ushio-Fukai, M. Yamaoka-Tojo, S. Ikeda, N. Patrushev, and R. W. Alexander Role of gp91phox (Nox2)-Containing NAD(P)H Oxidase in Angiogenesis in Response to Hindlimb Ischemia Circulation, May 10, 2005; 111(18): 2347 - 2355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Gruionu, J. B. Hoying, A. R. Pries, and T. W. Secomb Structural remodeling of mouse gracilis artery after chronic alteration in blood supply Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2047 - H2054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Frantz, K. A. Vincent, O. Feron, and R. A. Kelly Innate Immunity and Angiogenesis Circ. Res., January 7, 2005; 96(1): 15 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wang, O. A. Carretero, X.-Y. Yang, N.-E. Rhaleb, Y.-H. Liu, T.-D. Liao, and X.-P. Yang N-acetyl-seryl-aspartyl-lysyl-proline stimulates angiogenesis in vitro and in vivo Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2099 - H2105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Bendeck Macrophage Matrix Metalloproteinase-9 Regulates Angiogenesis in Ischemic Muscle Circ. Res., February 6, 2004; 94(2): 138 - 139. [Full Text] [PDF]
|
|