Homocysteine modulates the proteolytic potential of human vascular endothelial cells.
Pathological levels of homocysteine induce a metalloproteinase-dependent degradation of the elastic structures in arterial wall. This elastolytic process is preferentially localized toward the internal elastic laminae and in the first layers of the media, suggesting endothelium could participate in extracellular matrix degradation induced by homocysteine. Therefore, we studied the effects of homocysteine on proteolytic potential of endothelial cells. Human umbilical vein endothelial cells were cultured with concentrations of homocysteine matching human physiological (10 microM) and pathological (50, 100, and 250 microM) plasma homocysteine levels. Pathological levels of homocysteine increased the secretion of elastolytic metalloproteinase-2 and -9, but not of metalloproteinase-3 and -7. Homocysteine also increased the expression of human tissue kallikrein, a potential activator of matrix metalloproteinase-2 and -9, while the expression of urokinase plasminogen activator was not altered. These results suggest vascular endothelial cells could participate in the subendothelial degradation of the arterial elastic structures occurring in hyperhomocysteinemia.
Laboratory of Biochemistry, INSERM U 608, School of Pharmacy, University of the Mediterranean, Marseille, France.
Marielle
M
Chaussalet
Edouard
E
Lamy
Alexandrine
A
Foucault-Bertaud
Cecile
C
Genovesio
Florence
F
Sabatier
Françoise
F
Dignat-George
Philippe
P
Charpiot
D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D010450:Endopeptidases / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism
D006710:Homocysteine; D010450:Endopeptidases; D012697:Serine Endopeptidases; D020782:Matrix Metalloproteinases