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 non-pregnant, normal pregnant and pre-eclamptic women in the absence and presence of GM6001 (5 microM; 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 > or =70 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 non-pregnant 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.