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.
- Author:
Wei ZHENG
1
;
Xiang-Hong YANG
Author Information
- Publication Type:Journal Article
- MeSH: Anticholesteremic Agents; pharmacology; Cell Line, Tumor; Cells, Cultured; Coculture Techniques; Endothelial Cells; cytology; metabolism; Enzyme Precursors; metabolism; Gelatinases; metabolism; Humans; Leukemia, Monocytic, Acute; pathology; Matrix Metalloproteinase 2; metabolism; Metalloendopeptidases; metabolism; Monocytes; cytology; metabolism; Pravastatin; pharmacology; Tissue Inhibitor of Metalloproteinase-2; metabolism; Umbilical Veins; cytology
- From: Chinese Journal of Pathology 2005;34(2):105-108
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSA 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.
RESULTSCompared 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.
CONCLUSIONSInteraction 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.