## 5 Collagen Type I and III Turnover in Normal Pregnancy
### TIMP-1 and TIMP-2 Dysregulation
TIMP-1 levels were significantly reduced in the preeclampsia group at 26 weeks (\(p\) = 0.0002), but TIMP-2 levels were not quantifiable. Authors conclude that at all three gestational time points an imbalance in the MMP-2/TIMP-1 ratio was found in patients who subsequently developed preeclampsia\" [63]. In a cross-sectional study, [PERSON] et al., 2008, compared circulating levels of Pro-MMP-2, Pro-MMP-9, TIMP-1, TIMP-2, and the Pro-MMP-9/TIMP-1 and Pro-MMP-2/TIMP-2 ratios in women with preeclampsia, gestational hypertension, normotensive pregnancies and healthy nonpregnant women. Pro-MMP and TIMP concentrations were measured in plasma samples by gelatin zymography and ELISA. Higher TIMP-1 levels were found in PE compared with GH and normotensive pregnant women. Nonpregnant women had lower TIMP-2 levels than those found in normotensive pregnant controls, gestational hypertension and preeclampsia [64]. [PERSON] et al., 2012, examined whether two functional polymorphisms (g-1306 C \(>\) T and g-735 C \(>\) T) in MMP-2 gene are associated with preeclampsia or gestational hypertension, and whether they modify MMP-2 or TIMP-2 plasma concentrations in these hypertensive disorders of pregnancy. Plasma MMP-2 and TIMP-2 concentrations were measured by ELISA. \"The main findings were that pregnant women with preeclampsia had higher plasma MMP-2 and TIMP-2 concentrations than healthy pregnant (\(p\) < 0.05), although the MMP-2/TIMP-2 ratios were similar (\(p\) > 0.05). Moreover, pregnant women with gestational hypertension had elevated plasma MMP-2 levels and MMP-2/TIMP-2 ratios compared to healthy pregnant (\(p\) < 0.05)\" [65]. In a case-control study, [PERSON] et al., 2012, examined the total levels of MMP-9 and TIMP-1 and 2 in women with gestational hypertension and normotensive pregnant women. ELISA was used for evaluation of these biomarkers. TIMP-1 and TIMP-2 levels showed low levels of expression in the gestational hypertension group. Weak positive correlations were found on correlation analysis between maternal age and TIMP-1 in the gestational hypertension group and between gestational age and TIMP-2 in the control group [66]. In 2014, Early Pregnancy Prediction of Preeclampsia in Nulliparous Women, Combining Clinical Risk and Biomarkers The Screening for Pregnancy Endpoints (SCOPE) International Cohort Study investigated 47 biomarkers involved in the pathogenesis of preeclampsia. These biomarkers were measured in plasma sampled at 14 to 16 weeks' gestation from 5623 women. Considering TIMPs--higher levels of TIMP-1--101 ng/mL compared with the no preeclampsia group 91 ng/mL (\(p\) = 0.01) were reported [67]. [PERSON] et al., 2009, evaluated MMP-2 and -9, along with their inhibitors TIMP-1 and -2 in preeclamptic compared with normotensive pregnant and non-pregnant women. A sandwich enzyme-linked immunosorbent assay was used to measure MMPs and TIMPs. The serum levels of TIMP-1 were significantly higher in preeclamptic compared with both non-pregnant and normotensive pregnant women. TIMP-2 values were higher in normotensive pregnant and preeclamptic women compared with non-pregnant women. Results of the present investigation confirm that MMP-2 and TIMP-1 values are significantly higher in preeclampsia [68]. Tables 2 and 3 summarize the available literature data for studies measuring levels of TIMP-1 and TIMP-2 in samples of patients with hypertensive disorders of pregnancy.