## 5 Collagen Type I and III Turnover in Normal Pregnancy
### TIMP-1 and TIMP-2 Dysregulation  
According to [PERSON] et al., 2016, there was no significant difference in the levels of MMP-1, TIMP-1, and ratio of MMP-1 and TIMP-1 in pre-eclamptic and normal pregnancy females. There is a lack of alteration in the levels of MMP-1, TIMP-1, and their ratio during the progression of pre-eclampsia when compared with normal pregnancy [57]. \begin{table}
\begin{tabular}{c c c c c} \hline \hline \multirow{2}{*}{**Authors**} & \multicolumn{2}{c}{**Hypertenasive**} & \multirow{2}{*}{**Sample Type**} & \multirow{2}{*}{**Method**} & \multirow{2}{*}{**Main Findings**} \\  & **Disorders of** & & & \\  & **Pregnancy Type** & & & \\ \hline [PERSON] et al. [56] & PE & Plasma & \begin{tabular}{c} Zymograph \\ ELISA \\ \end{tabular} & \begin{tabular}{c} Increased expression in \\ systemic vessels Increased \\ MMP-1 levels \\ \end{tabular} \\ [PERSON] et al. [57] & PE & Serum & ELISA & Non significant difference in \\ [PERSON] et al. [58] & PE & \begin{tabular}{c} Aorta, uterus, \\ placenta \\ \end{tabular} & \begin{tabular}{c} Zymography \\ \end{tabular} & \
\begin{tabular}{c} Increased MMP-1 expression \\ in aorta, uterus and placenta \\ of rats \\ \end{tabular} \\ [PERSON] et al. [59] & PE &
\begin{tabular}{c} Maternal umbilical \\ serum \\ \end{tabular} & ELISA & Decreased MMP-1 levels \\ \hline MMP-1—matrix metalloproteinase 1, HDP—hypertensive disorders of pregnancy, PE—precLampsia, ELISA—enzyme linked immunosorbent assay. & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Levels of matrix metalloproteinase 1 (MMP-1) in samples of patients with hypertensive disorders of pregnancy. MMP-9, TIMP-1 polymorphism, plasma TIMP-1 levels, and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy are examined by [PERSON] et al., 2014. Plasma MMP-9 and TIMP-1 levels were measured by ELISA. Gestational hypertension patients with the GG genotype for the TIMP-1 polymorphism had lower MMP-9 levels and MMP-9/TIMP-1 ratios than those with the TT genotype. Preeclampsia patients with the TG genotype had higher TIMP-1 levels [61]. [PERSON] et al., 2005, investigated circulating MMP-9 and TIMP-1 and -2 levels in women with gestational hypertension, normotensive women with normal pregnancies and healthy nonpregnant control subjects. Plasma MMP-9, TIMP-1, and TIMP-2 were measured by ELISA. 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. Plasma TIMP-1 in non-pregnant was 197 \(\pm\) (ng/mL) vs. normotensive pregnant 180 \(\pm\) (ng/mL) vs. gestational hypertension 195 (ng/mL) (\(p\) = 0.006). Plasma TIMP-2 in non-pregnant was 140 \(\pm\) (ng/mL) vs. normotensive pregnant 138\(\pm\) (ng/mL) vs. gestational hypertension 180 \(\pm\)s (ng/mL) (\(p\) = 0.007) Authors concluded that \"altered MMP/TIMP ratios in maternal blood during gestational hypertension. 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, investigators suggest that these observations may be related to the pathophysiology of human gestational hypertension\" [62]. [PERSON] et al., 2016 [57], compared the serum values of MMP-1, TIMP-1, and their ratio in the second and third trimester of normal and preeclampsia pregnancy. ELISA was used for determination of MMP-1 and TIMP-1. There is a lack of alteration in the levels of MMP-1, TIMP-1, and their ratio during the progression of preeclampsia when compared with normal pregnancy. [PERSON] et al., 2005, examined MMP-2 and-9 levels, TIMP-1 and TIMP-2 in the plasma of women who subsequently develop preeclampsia. Plasma samples were taken from women whose pregnancies were subsequently complicated by preeclampsia and from normal pregnant women at 22 and 26 weeks and at delivery or diagnosis. \"Following equal protein loading, MMP-2 and 9 and TIMP-1 and 2 were quantified using zymography and Western blot analysis, respectively.