Frizzled A, a novel angiogenic factor: promises for cardiac repair.
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 microm2 in control; P<0.001).


CONCLUSIONS
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.
Barandon
Laurent
L
Pr Deville Department of Cardio-Vascular Surgery, Haut-Lévêque Hospital, Pessac 33604, France. lesbarandon@wanadoo.fr
Couffinhal
Thierry
T
Dufourcq
Pascale
P
Ezan
Jérome
J
Costet
Pierre
P
Daret
Danièle
D
Deville
Claude
C
Duplàa
Cécile
C
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D002921:Cicatrix / Q000378:metabolism; D006342:Heart Rupture, Post-Infarction / Q000517:prevention & control*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D000094742:Secreted Frizzled-Related Proteins
D043925:Angiogenesis Inducing Agents; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C485539:Sfrp1 protein, mouse; D000094742:Secreted Frizzled-Related Proteins