METALLOPROTEINASE ACTIVITY IN MAMMARY ART ERIES AND SAPHENOUS VEINS -MODIFICATION BY DOXYCYCLINE

Background: Alterations in the synthesis and degradation of extracellu lar matrix occur during atherogenesis. Metalloproteinases, whose activ ity may be inhibited with doxycicline in other tissues, play an import ant role in this process. Aims: 1. To characterize metalloproteinases activities in internal mammary artery and saphenous vein, and 2. To as sess the effect of doxycicline in the activity of metalloproteinases o f 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. Metalloprote inases 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 m etalloproteinase-9 activity by 207% and metalloproteinase-2 by 290%. W estern Blot analysis showed that doxycicline also inhibited metallopro teinase-1 expression. In cultured smooth muscle cells, the median inhi bitory concentration of doxycicline for metalloproteinase-2 was 138 mu M (r(2)=0.82). Conclusions: Internal mammary arteries and saphenous v eins have different metalloproteinase activities, that are inhibited b y doxycicline.