Comparative assessment of matrix metalloproteinase (MMP)-2 and MMP-9, and their inhibitors, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in preeclampsia and gestational hypertension Ana C.T. Palei a , Valeria C. Sandrim b , Ricardo C. Cavalli c , Jose E. Tanus-Santos b, ⁎ a Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 13081-970, Campinas, SP, Brazil b Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil c Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil Received 17 January 2008; received in revised form 4 April 2008; accepted 19 April 2008 Available online 26 April 2008 Abstract Objectives: To compare the circulating levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2, and the MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in preeclampsia and gestational hypertension with those found in normotensive pregnancies. Design and methods: We studied 83 pregnant women (30 healthy pregnant women with uncomplicated pregnancies, 26 with gestational hypertension, and 27 with preeclampsia) and 30 healthy nonpregnant women in a cross-sectional study. MMP and TIMP concentrations were measured in plasma samples by gelatin zymography and ELISA, respectively. Results: We found higher plasma pro-MMP-9 levels, and higher pro-MMP-9/TIMP-1 ratios in women with gestational hypertension (95%-CI: 1.031 to 2.357, and 0.012 to 0.031, respectively), but not with preeclampsia, compared with those found in normotensive pregnant women (95%-CI: 0.810 to 1.350, and 0.006 to 0.013, respectively; both P b 0.05). We found no significant differences in pro-MMP-2 levels (P N 0.05). Conclusions: The higher net MMP-9 (but not MMP-2) activity in gestational hypertension compared with normotensive pregnancy suggests that MMP-9 plays a role in the pathophysiology of gestational hypertension. Conversely, the lack of such alterations in preeclampsia is consistent with the notion that different pathophysiological mechanisms are involved in these hypertensive disorders. © 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Keywords: Gestational hypertension; Metalloproteinases; Preeclampsia; TIMPs Introduction Hypertensive disorders are common complications affecting 5% to 10% of pregnancies [1] and a major cause of preterm delivery [2]. While various hypotheses have been explored to explain pregnancy-induced hypertension (PIH; which includes preeclampsia and gestational hypertension) and chronic hyper- tension, the pathophysiology of these conditions remains to be determined [3]. In this regard, there is growing evidence sug- gesting that decreased activity of matrix metalloproteinases (MMPs) could result in poor trophoblast invasion of maternal spiral arteries, thus leading to poor fetoplacental unit perfusion and release of placental factors that affect the vascular tone and remodeling [4]. In addition, it has recently been suggested that MMPs (especially MMP-2) play a greater role in mediating vasodilation in preeclamptic pregnancies compared with nor- motensive pregnancies [5]. Together, these findings are con- sistent with the notion that MMPs play significant roles in both acute and chronic regulation of the cardiovascular system [6]. Giving support to these previous reports, a few clinical studies described changes in the circulating levels of MMPs (especially MMP-2 and MMP-9) and their endogenous inhibitors (tissue inhibitors of metalloproteinases; TIMPs) in women with PIH [7–10]. This is important because measuring the plasma levels Available online at www.sciencedirect.com Clinical Biochemistry 41 (2008) 875 – 880 ⁎ Corresponding author. Fax: +55 16 3633 2301. E-mail addresses: tanus@fmrp.usp.br, tanussantos@yahoo.com (J.E. Tanus-Santos). 0009-9120/$ - see front matter © 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.clinbiochem.2008.04.015