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Eur J Cardiothorac Surg 2004;25:76-83
© 2004 Elsevier Science NL


Frizzled A, a novel angiogenic factor: promises for cardiac repair

Laurent Barandona,b*, Thierry Couffinhalb,c, Pascale Dufourcqb, Jérome Ezanb, Pierre Costetd, Danièle Daretb, Claude Devillea, Cécile Duplàab

a Pr Deville Department of Cardio-Vascular Surgery, Haut-Lévêque Hospital, Pessac 33604, France
b National Health Institut and Medical Research, INSERM U441, 33600 Pessac, France
c Department of Cardiology, Haut-Lévêque Hospital, Pessac 33604, France
d Center for Transgene Technology, University of Bordeaux 2, 33000 Bordeaux, France

Received 3 March 2003; received in revised form 31 July 2003; accepted 7 August 2003.

* Corresponding author. Tel.: +33-5-5765-6565; fax: +33-5-5636-8979
e-mail: lesbarandon{at}wanadoo.fr

Objective: Frizzled A is a very recent protein expressed in the cardiovascular hood by cardiomyocytes and by endothelial cells. This protein plays key roles in vitro in vascular cell proliferation and is able to induce an in vivo angiogenic response. Regarding these properties, we assess the hypothesis that Frizzled A could act in the healing process after myocardial infarction. Methods: To investigate the role of Frizzled A, we established a transgenic mouse line overexpressing the protein and developed a model of myocardial infarction by coronary artery ligation. Results: The incidence of cardiac rupture after myocardial infarction was reduced in transgenic mice (6.5 versus 26.4% in controls, n=165; P<0.01). Infarct sizes were smaller in transgenic mice (18% of left ventricle circumference versus 28.1% in control at day 30; P<0.001; n=6) and the cardiac function was improved (3800±370 versus 2800±840 mmHg/s dp/dtmax in controls, -2800±440 versus -1800±211 dp/dtmin in controls at day 15; P<0.001; n=6). Early leukocyte infiltration had decreased in transgenic mice during the first week (103±59 versus 730±463 cells/mm2 in controls at day 7; P<0.001; n=6) and the apoptotic index was decreased by 50% at day 7. Capillary density in the scar was higher in transgenic mice (290±103 versus 104±43 vessels/mm2 in control at day 15; P<0.001) and vessels were more muscularized and mean lumen area was 3-fold higher (952±902 versus 313±350 µm2 in control; P<0.001). Conclusion: Overexpression of Frizzled A reduced the infarct size, improved cardiac recovery, modified inflammatory response and amplified angiogenesis. For these reasons, this protein would be of interest for cardiac surgeons using angiogenic therapy (as gene or protein injection) in ischemic heart diseases in non-revascularizable patients.

Key Words: Myocardial infarction • Angiogenesis • Inflammatory cell • Gene therapy




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