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The role of matrix metalloproteinases in vascular function: implications for normal pregnancy and pre‐eclampsia
Author(s) -
Merchant Shaila J.,
Davidge Sandra T.
Publication year - 2004
Publication title -
bjog: an international journal of obstetrics and gynaecology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.157
H-Index - 164
eISSN - 1471-0528
pISSN - 1470-0328
DOI - 10.1111/j.1471-0528.2004.00223.x
Subject(s) - eclampsia , medicine , endocrinology , matrix metalloproteinase , preeclampsia , pregnancy , myogenic contraction , biology , smooth muscle , genetics
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 μM; 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 ≥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.