on October 27, 2003
Published online before print October 27, 2003, doi: 10.1161/01.CIR.0000093186.22847.4C
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on January 28, 2003
From the Department of Cardiovascular Surgery and Cardiology (L.B., T.C., L.L.), Hôpital Haut Lévêque, Pessac; the Institut National de la Santé et de la Recherche Médicale U441 (L.B., T.C., J.E., P.D., P.A., L.L., C.M., D.D., C.D.), Pessac; and the Center for Transgene Technology (P.C.), University of Bordeaux, Bordeaux, France. * To whom correspondence should be addressed. E-mail: thierry.couffinhal{at}bordeaux.inserm.fr.
Background--FrzA/sFRP-1, a secreted, frizzled-related protein and antagonist for the wnt/frizzled pathway, is expressed in the heart and vessels during mouse embryogenesis and adulthood. FrzA is involved in cell cycle control of vascular cells and angiogenesis. We assessed the hypothesis that FrzA could control the healing process after myocardial infarction (MI). Methods and Results--We demonstrated an upregulation of sFRP-1 and distinct wnt and fz member expression after MI. We established transgenic (Tg) mice that overexpress FrzA under a cytomegalovirus promoter and developed a model of MI by coronary artery ligation. FrzA reduced cardiac rupture after MI in Tg (6.5% versus 26.4% in controls; n=165, P<0.01). MI was smaller in Tg at each time point (18±10.8% of left ventricular circumference versus 30±14.2% in controls at day 30; P<0.001). Similar results were found in cryolesion-induced MI. Cardiac function was improved in Tg mice (3800±370 mm Hg/s dP/dtmax versus 2800±840 in controls; -2800±440 dP/dtmin versus -1800±211 in controls at day 15; P<0.001). Early leukocyte infiltration had decreased in Tg mice during the first week. Apoptotic index was decreased by 50% in Tg mice at day 7. Matrix metalloproteinase-2 and -9 activity was reduced in Tg mice at day 4, and collagen deposition in the scar was increased in Tg mice. Capillary density in the scar was higher in Tg mice (290±103 vessels/mm2 versus 104±43 in controls at day 15; P<0.001). Vessels were more muscularized, and mean lumen area was 3-fold higher in Tg animals. Conclusions--Overexpression of FrzA, through direct or indirect interaction with different phases of infarct healing, reduced infarct size and improved cardiac function.
Revised on June 27, 2003
Accepted on June 30, 2003
Reduction of Infarct Size and Prevention of Cardiac Rupture in Transgenic Mice Overexpressing FrzA
Laurent Barandon MD,
Key words: myocardial infarction • remodeling • collagen • angiogenesis
This article has been cited by other articles:
 |
|
 |
|
  T. Moore-Morris, A. Varrault, M. E. Mangoni, A. Le Digarcher, V. Negre, C. Dantec, L. Journot, J. Nargeot, and B. Couette Identification of Potential Pharmacological Targets by Analysis of the Comprehensive G Protein-Coupled Receptor Repertoire in the Four Cardiac Chambers Mol. Pharmacol., May 1, 2009; 75(5): 1108 - 1116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Lewin, M. Matus, A. Basu, K. Frebel, S. P. Rohsbach, A. Safronenko, M. D. Seidl, F. Stumpel, I. Buchwalow, S. Konig, et al. Critical Role of Transcription Factor Cyclic AMP Response Element Modulator in {beta}1-Adrenoceptor-Mediated Cardiac Dysfunction Circulation, January 6, 2009; 119(1): 79 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Romaker, M. Puetz, S. Teschner, J. Donauer, M. Geyer, P. Gerke, B. Rumberger, B. Dworniczak, P. Pennekamp, B. Buchholz, et al. Increased Expression of Secreted Frizzled-Related Protein 4 in Polycystic Kidneys J. Am. Soc. Nephrol., January 1, 2009; 20(1): 48 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Zelarayan, C. Noack, B. Sekkali, J. Kmecova, C. Gehrke, A. Renger, M.-P. Zafiriou, R. van der Nagel, R. Dietz, L. J. de Windt, et al. {beta}-Catenin downregulation attenuates ischemic cardiac remodeling through enhanced resident precursor cell differentiation PNAS, December 16, 2008; 105(50): 19762 - 19767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Aicher, O. Kollet, C. Heeschen, S. Liebner, C. Urbich, C. Ihling, A. Orlandi, T. Lapidot, A. M. Zeiher, and S. Dimmeler The Wnt Antagonist Dickkopf-1 Mobilizes Vasculogenic Progenitor Cells via Activation of the Bone Marrow Endosteal Stem Cell Niche Circ. Res., October 10, 2008; 103(8): 796 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Derval, L. Barandon, P. Dufourcq, L. Leroux, J.-M. D. Lamaziere, D. Daret, T. Couffinhal, and C. Duplaa Epicardial deposition of endothelial progenitor and mesenchymal stem cells in a coated muscle patch after myocardial infarction in a murine model. Eur. J. Cardiothorac. Surg., August 1, 2008; 34(2): 248 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Hinkel, C. El-Aouni, T. Olson, J. Horstkotte, S. Mayer, S. Muller;, M. Willhauck, C. Spitzweg, F.-J. Gildehaus, W. Munzing, et al. Thymosin {beta}4 Is an Essential Paracrine Factor of Embryonic Endothelial Progenitor Cell-Mediated Cardioprotection Circulation, April 29, 2008; 117(17): 2232 - 2240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Nathan, A. Monovich, L. Tirosh-Finkel, Z. Harrelson, T. Rousso, A. Rinon, I. Harel, S. M. Evans, and E. Tzahor The contribution of Islet1-expressing splanchnic mesoderm cells to distinct branchiomeric muscles reveals significant heterogeneity in head muscle development Development, February 15, 2008; 135(4): 647 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Dufourcq, L. Leroux, J. Ezan, B. Descamps, J.-M. D. Lamaziere, P. Costet, C. Basoni, C. Moreau, U. Deutsch, T. Couffinhal, et al. Regulation of Endothelial Cell Cytoskeletal Reorganization by a Secreted Frizzled-Related Protein-1 and Frizzled 4- and Frizzled 7-Dependent Pathway: Role in Neovessel Formation Am. J. Pathol., January 1, 2008; 172(1): 37 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Arab, I. E. Konstantinov, C. Boscarino, E. Cukerman, A. Mori, J. Li, P. P. Liu, A. N. Redington, and J. G. Coles Early gene expression profiles during intraoperative myocardial ischemia-reperfusion in cardiac surgery J. Thorac. Cardiovasc. Surg., July 1, 2007; 134(1): 74 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fielitz, E. van Rooij, J. A. Spencer, J. M. Shelton, S. Latif, R. van der Nagel, S. Bezprozvannaya, L. de Windt, J. A. Richardson, R. Bassel-Duby, et al. Loss of muscle-specific RING-finger 3 predisposes the heart to cardiac rupture after myocardial infarction PNAS, March 13, 2007; 104(11): 4377 - 4382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Singh, F.-Q. Li, T. Hamazaki, H. Kasahara, K.-I. Takemaru, and N. Terada Chibby, an Antagonist of the Wnt/{beta}-Catenin Pathway, Facilitates Cardiomyocyte Differentiation of Murine Embryonic Stem Cells Circulation, February 6, 2007; 115(5): 617 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Couffinhal, P. Dufourcq, and C. Duplaa {beta}-Catenin Nuclear Activation: Common Pathway Between Wnt and Growth Factor Signaling in Vascular Smooth Muscle Cell Proliferation? Circ. Res., December 8, 2006; 99(12): 1287 - 1289. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Brade, J. Manner, and M. Kuhl The role of Wnt signalling in cardiac development and tissue remodelling in the mature heart Cardiovasc Res, November 1, 2006; 72(2): 198 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Y. Hahn, H.-J. Cho, J.-W. Bae, H.-S. Yuk, K.-i. Kim, K.-W. Park, B.-K. Koo, I.-H. Chae, C.-S. Shin, B.-H. Oh, et al. beta-Catenin Overexpression Reduces Myocardial Infarct Size through Differential Effects on Cardiomyocytes and Cardiac Fibroblasts J. Biol. Chem., October 13, 2006; 281(41): 30979 - 30989. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Lindsey, G. P. Escobar, R. Mukherjee, D. K. Goshorn, N. J. Sheats, J. A. Bruce, I. M. Mains, J. K. Hendrick, K. W. Hewett, R. G. Gourdie, et al. Matrix Metalloproteinase-7 Affects Connexin-43 Levels, Electrical Conduction, and Survival After Myocardial Infarction Circulation, June 27, 2006; 113(25): 2919 - 2928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Barandon, P. Dufourcq, P. Costet, C. Moreau, C. Allieres, D. Daret, P. D. Santos, J.-M. D. Lamaziere, T. Couffinhal, and C. Duplaa Involvement of FrzA/sFRP-1 and the Wnt/Frizzled Pathway in Ischemic Preconditioning Circ. Res., June 24, 2005; 96(12): 1299 - 1306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Masaki, M. Izumi, Y. Oshima, Y. Nakaoka, T. Kuroda, R. Kimura, S. Sugiyama, K. Terai, M. Kitakaze, K. Yamauchi-Takihara, et al. Smad1 Protects Cardiomyocytes From Ischemia-Reperfusion Injury Circulation, May 31, 2005; 111(21): 2752 - 2759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sun, F. Dawood, W.-H. Wen, M. Chen, I. Dixon, L. A. Kirshenbaum, and P. P. Liu Excessive Tumor Necrosis Factor Activation After Infarction Contributes to Susceptibility of Myocardial Rupture and Left Ventricular Dysfunction Circulation, November 16, 2004; 110(20): 3221 - 3228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Barandon, T. Couffinhal, P. Dufourcq, P. Alzieu, D. Daret, C. Deville, and C. Duplaa Repair of Myocardial Infarction by Epicardial Deposition of Bone Marrow Cell-Coated Muscle Patch in a Murine Model Ann. Thorac. Surg., October 1, 2004; 78(4): 1409 - 1417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ezan, L. Leroux, L. Barandon, P. Dufourcq, B. Jaspard, C. Moreau, C. Allieres, D. Daret, T. Couffinhal, and C. Duplaa FrzA/sFRP-1, a secreted antagonist of the Wnt-Frizzled pathway, controls vascular cell proliferation in vitro and in vivo Cardiovasc Res, September 1, 2004; 63(4): 731 - 738. [Abstract] [Full Text] [PDF]
|
|