Decreased PGE2 content reduces MMP-1 activity and consequently increases collagen density in human varicose vein

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Abstract

Varicose veins are elongated and dilated saphenous veins. Despite the high prevalence of this disease, its pathogenesis remains unclear. Aims: In this study, we investigated the control of matrix metalloproteinases (MMPs) expression by prostaglandin (PG)E2 during the vascular wall remodeling of human varicose veins. Methods and Results: Varicose (small (SDv) and large diameter (LDv)) and healthy saphenous veins (SV) were obtained after surgery. Microsomal and cytosolic PGE-synthases (mPGES and cPGES) protein and mRNA responsible for PGE2 metabolism were analyzed in all veins. cPGES protein was absent while its mRNA was weakly expressed. mPGES-2 expression was similar in the different saphenous veins. mPGES-1 mRNA and protein were detected in healthy veins and a significant decrease was found in LDv. Additionally, 15-hydroxyprostaglandin dehydrogenase (15-PGDH), responsible for PGE2 degradation, was over-expressed in varicose veins. These variations in mPGES-1 and 15-PGDH density account for the decreased PGE 2 level observed in varicose veins. Furthermore, a significant decrease in PGE2 receptor (EP4) levels was also found in SDv and LDv. Active MMP-1 and total MMP-2 concentrations were significantly decreased in varicose veins while the tissue inhibitors of metalloproteinases (TIMP -1 and -2), were significantly increased, probably explaining the increased collagen content found in LDv. Finally, the MMP/TIMP ratio is restored by exogenous PGE2 in varicose veins and reduced in presence of an EP4 receptor antagonist in healthy veins. Conclusions: In conclusion, PGE2 could be responsible for the vascular wall thickening in human varicose veins. This mechanism could be protective, strengthening the vascular wall in order to counteract venous stasis. © 2014 Gomez et al.

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Gomez, I., Benyahia, C., Louedec, L., Leséche, G., Jacob, M. P., Longrois, D., & Norel, X. (2014). Decreased PGE2 content reduces MMP-1 activity and consequently increases collagen density in human varicose vein. PLoS ONE, 9(2). https://doi.org/10.1371/journal.pone.0088021

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