[Synthesis of collagen in culture of endothelial cells of the human umbilical vein. Effects of cyclosporine A].
Interstitial renal fibrosis and gingival hypertrophy are frequent side-effects of cyclosporin A which have been attributed to a dysfunction of extracellular matrix synthesis. Endothelial cells might participate in the matrix accumulation observed. We studied the effects of increasing concentrations of cyclosporin A on protein synthesis by human umbilical vein endothelial cells. Collagen synthesis decreased significantly to 800 ng/ml in both medium and cell layer. The percentage of hydroxylation of its proline residues decreased significantly as from 400 ng/ml. The main proteins, analysed by SDS-PAGE, were thrombospondin, fibronectin and the alpha 1 and alpha 2 chains of type IV collagen. These fractions did not show any change after 24 hours exposure to 200 ng/ml of cyclosporin A. These results demonstrate an inhibitory effect of cyclosporin A on collagen synthesis by human umbilical vein endothelial cells. Consequently, matrix accumulation by increased collagen synthesis in cyclosporin A treated patient may not be directly related to the drug effect on endothelial cells.
Fakir
M
M
Néphrologie Transplantation Rénale, CHU, Reims.
Wegrowski
J
J
Bour
P
P
Joundi
A
A
Chanard
J
J
Maquart
F X
FX
D003094:Collagen / Q000096:biosynthesis*; D016572:Cyclosporine / Q000494:pharmacology*; D003864:Depression, Chemical; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism*
D016572:Cyclosporine; D003094:Collagen
Synthèse de collagène par les cellules endothéliales de veine ombilicale humaine en culture. Effets de la ciclosporine A.