The role of matrix metalloproteinases in vascular function: implications for normal pregnancy and pre-eclampsia

Objectives (1) To investigate the effects of plasma from non-pregnant, normal pregnant and pre-eclamptic women on myogenic tone and endothelium-dependent relaxation; (2) To investigate the role of matrix metalloproteinases (MMPs) in these parameters of vascular function. Design Analysis of the effects of plasma from non-pregnant, normal pregnant and pre-eclamptic women on myogenic tone and endothelium-dependent relaxation, and the effects of MMP inhibition on these parameters. Setting University of Alberta, Edmonton, Alberta, Canada. Samples Pooled plasma from non-pregnant (n = 9), normal pregnant (n = 6) and pre-eclamptic women (n = 12). Methods Mesenteric arteries from virgin female C57BL/6J mice were exposed to pooled plasma from nonpregnant, normal pregnant and pre-eclamptic women in the absence and presence of GM6001 (5 muM; MMP inhibitor), and arterial function was assessed. Main outcome measures Myogenic tone and endothelium-dependent relaxation. Results Plasma of women with pre-eclampsia, and interestingly, plasma of non-pregnant women, significantly enhanced myogenic tone at pressures greater than or equal to70 mmHg (P < 0.001) and blunted the maximum relaxation to methacholine (P < 0.001; P < 0.005) in isolated arteries. GM6001 altered response only in vessels exposed to the plasma of women with pre-eclampsia; however, contrary to our hypothesis, this further enhanced myogenic tone and further abrogated relaxation. Conclusions The strikingly similar vascular function profiles of vessels incubated in the plasma of nonpregnant and pre-eclamptic women suggest that pre-eclampsia may be due, in part, to the lack of a necessary adaptation to pregnancy. Despite these similarities, however, there are differential effects of MMP inhibition, suggesting that MMPs play a greater role in the vasculature of women with pre-eclampsia compared with non-pregnant and normal pregnant women.