Circulating matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 and -2 levels in gestational hypertension

Muzahir H. Tayebjee, Ioannis Karalis, Sunil K. Nadar, D. Gareth Beevers, Robert J. MacFadyen, Gregory Y H Lip

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)325-329
Number of pages5
JournalAmerican Journal of Hypertension
Volume18
Issue number3
DOIs
Publication statusPublished - Mar 2005

Fingerprint

Tissue Inhibitor of Metalloproteinase-2
Pregnancy Induced Hypertension
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 9
Blood Pressure
Extracellular Matrix
Mothers
Pregnancy
Parity
Matrix Metalloproteinases
Gestational Age
Blood Vessels
Pregnant Women
Enzyme-Linked Immunosorbent Assay
Regression Analysis
Hypertension

Keywords

  • Gestational hypertension
  • Matrix metalloproteinases
  • Tissue inhibitor of metalloproteinases

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Circulating matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 and -2 levels in gestational hypertension. / Tayebjee, Muzahir H.; Karalis, Ioannis; Nadar, Sunil K.; Beevers, D. Gareth; MacFadyen, Robert J.; Lip, Gregory Y H.

In: American Journal of Hypertension, Vol. 18, No. 3, 03.2005, p. 325-329.

Research output: Contribution to journalArticle

Tayebjee, Muzahir H. ; Karalis, Ioannis ; Nadar, Sunil K. ; Beevers, D. Gareth ; MacFadyen, Robert J. ; Lip, Gregory Y H. / Circulating matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 and -2 levels in gestational hypertension. In: American Journal of Hypertension. 2005 ; Vol. 18, No. 3. pp. 325-329.
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abstract = "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.",
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T1 - Circulating matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 and -2 levels in gestational hypertension

AU - Tayebjee, Muzahir H.

AU - Karalis, Ioannis

AU - Nadar, Sunil K.

AU - Beevers, D. Gareth

AU - MacFadyen, Robert J.

AU - Lip, Gregory Y H

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N2 - 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.

AB - 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.

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