In vivo electrotransfer of interleukin-10 cDNA prevents endothelial upregulation of activated NF-kappaB and adhesion molecules following an atherogenic diet.
OBJECTIVE
Interleukin (IL)-10 has anti-atherogenic properties. However, the molecular mechanisms involved in IL-10 protection against atherosclerosis in vivo remain poorly understood. In this study, we examined the effect of IL-10 cDNA in vivo electrotransfer on diet-induced, endothelial activation.


METHODS
C57BL/6J mice were fed an atherogenic diet for 10 days. Expression of VCAM-1 and ICAM-1 was examined in the aortic sinus, a region predisposed to atherogenesis in mice, using immunohistochemistry. NF-kappaB activation was examined using a monoclonal antibody that selectively reacts with the activated form of the p65 subunit.


RESULTS
We detected a low basal expression of activated NF-kappaB, VCAM-1 and ICAM-1 in the endothelium of the aortic sinus. Endothelial expression of activated NF-kappaB, VCAM-1 and ICAM-1 was markedly increased after 10 days on the atherogenic diet (p < 0.001). In vivo electrotransfer of a murine IL-10-encoding plasmid completely prevented diet-induced endothelial upregulation of activated NF-kappaB, VCAM-1 and ICAM-1 (p < 0.01).


CONCLUSIONS
In vivo electrotransfer of IL-10 cDNA prevents diet-induced endothelial activation. These results suggest that the protective effects of IL-10 may already occur in the very early stages of atherogenesis.
Potteaux
Stéphane
S
Centre de Recherche Cardiovasculaire Inserm Lariboisière, U689, Paris.
Deleuze
Virginie
V
Merval
Régine
R
Bureau
Michel F
MF
Esposito
Bruno
B
Scherman
Daniel
D
Tedgui
Alain
A
Mallat
Ziad
Z
D000818:Animals; D018076:DNA, Complementary; D004036:Diet, Atherogenic; D018274:Electroporation; D004727:Endothelium / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D018014:Gene Transfer Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000096:biosynthesis*; D012850:Sinus of Valsalva / Q000378:metabolism*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D018076:DNA, Complementary; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10