Background: Alterations in the synthesis and degradation of extracellular matrix occur during atherogenesis. Metalloproteinases, whose activity may be inhibited with doxycicline in other tissues, play an important role in this process.
Aims: 1. To characterize metalloproteinase activities in internal mammary artery and saphenous vein, and 2. To assess the effect of doxycicline in the activity of metalloproteinases of these vessels and of cultured smooth muscle cells.
Methods: Segments of internal mammary arteries and saphenous veins and cultured smooth muscle cells were incubated with and without doxycicline. Metalloproteinases activity was assessed by zymography and Western Blot.
Results: Activity of metalloproteinase-9 in saphenous veins was 217% less than in internal mammary arteries. In these vessels doxycicline decreased metalloproteinase-9 activity by 207% and metalloproteinase-2 by 290%. Western Blot analysis showed that docycicline also inhibited metalloproteinase-1 expression. In cultured smooth muscle cells, the median inhibitory concentration of doxycicline for metalloproteinase-2 was 138 microM (r2 = 0.82).
Conclusions: Internal mammary arteries and saphenous veins have different metalloproteinase activities, that are inhibited by doxycicline.