Circulating matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 and -2 levels in gestational hypertension.
BACKGROUND
Gestational hypertension (GH) is dangerous to both mother and child. Arterial invasiveness and growth are dependent on successful extracellular matrix (ECM) breakdown, which may be abnormal in GH. We hypothesized abnormalities in circulating matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1 and TIMP-2, respectively) in patients with GH, when compared with normotensive women with normal pregnancies and healthy nonpregnant control subjects.


METHODS
Plasma MMP-9, TIMP-1, and TIMP-2 were measured by ELISA in 23 women with GH, 30 normotensive pregnant women, and 28 nonpregnant women who were matched for age, gestational age, and parity.


RESULTS
Levels of circulating MMP-9, TIMP-1 and TIMP-2, and the MMP-9/TIMP-1 and MMP-9/TIMP-2 ratios were significantly different among the three groups (P = .026, P = .006, P = .007, P = .001 and P = .008 respectively). Within the GH group, MMP-9 and the MMP-9/TIMP-1 ratio correlated negatively with age (r = -0.581, P = .004 and r = -0.563, P = .005, respectively) and levels of diastolic blood pressure (r = -0.432, P = .040 and r = -0.461, P = .027, respectively). With multiple regression analysis, only age independently correlated with circulating levels of MMP-9 (P = .010); neither age nor levels of diastolic blood pressure had any effect on the MMP-9/TIMP-1 ratio.


CONCLUSIONS
We have demonstrated altered MMP/TIMP ratios in maternal blood during GH. These observations suggest pregnancy-related changes in ECM breakdown and turnover. Given the importance of changes in ECM composition to vascular and cardiac structure in hypertension, we suggest that these observations may be related to the pathophysiology of human GH.
Tayebjee
Muzahir H
MH
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, UK.
Karalis
Ioannis
I
Nadar
Sunil K
SK
Beevers
D Gareth
DG
MacFadyen
Robert J
RJ
Lip
Gregory Y H
GY
D000328:Adult; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000097:blood* / Q000503:physiopathology*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D011247:Pregnancy; D012044:Regression Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020780:Matrix Metalloproteinase 9