[Effects of interaction between vascular endothelial cells and monocytes on expression of matrix metalloproteinase-2 and of tissue inhibitor of metalloproteinases 2 and regulation of pravastatin].
OBJECTIVE
To analyze the effects of interaction between vascular endothelial cells and monocytes on the expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2), as well as the regulation of pravastatin.


METHODS
A co-cultured system of monocytes and endothelial cells was established through addition of THP-1 to human umbilical vein endothelial cells (HUVECs) in various rates. After 24 hours, the changes in activity and expression of MMP-2 and TIMP-2 in the co-culture system were studied by zymography and reverse zymography. The 1:1 co-culture system was selected and one control group (no pravastatin added) and experimental groups (with concentration of pravastatin being 0.1, 0.5 and 1.0 micromol/ml respectively) were studied. All groups were cultured for another 24 hours and analyzed in the same way.


RESULTS
Compared to the single cultured HUVECs, the activity of proMMP-2 in the co-cultured system increased by 2.09, 2.46 and 2.07 folds respectively (number = 8, P < 0.01). There was also activated MMP-2 secretion in the co-culture system. The secretion of proMMP-2 and active MMP-2 in the 1:1 co-cultured system was most obvious. After pravastatin treatment, the activity of proMMP-2 and MMP-2, decreased significantly (number = 8, P < 0.01). MMP-2 secretion was completely suppressed after 1.0 micromol/ml pravastatin treatment. Reverse zymography revealed that, compared to the single culture HUVECs or THP-1, the secretion of TIMP-2 decreased in the co-cultured system, regardless of the ratio of mixture. However, pravastatin had no obvious effect on TIMP-2.


CONCLUSIONS
Interaction between vascular endothelial cells and monocytes may contribute to the secretion and activation of MMP-2 and suppress secretion of TIMP-2. Pravastatin may inhibit the secretion and activation of MMP-2.
Zheng
Wei
W
Experimental Pathology Laboratory, China Medical University, Shenyang 110001, China.
Yang
Xiang-Hong
XH
D000924:Anticholesteremic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D017035:Pravastatin / Q000494:pharmacology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
D000924:Anticholesteremic Agents; D004792:Enzyme Precursors; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase; D020778:Matrix Metalloproteinase 2; D017035:Pravastatin