41 Circulating level of TIMP-4 is elevated in preeclampsia

Abstract

Introduction The MMPs (matrix metalloproteinases) and theirs endogenous inhibitors (proteins that bind MMP active sites preventing proteolytic cleavage of substrates: TIMP-1, -2, -3 and -4) play important roles in the cardiovascular system regulation and some studies have been demonstrated imbalance among MMPs and TIMPs in preeclampsia compared to healthy pregnancy. Even though the TIMPs present many similarities, they show several structural and biochemical differences. While the circulating levels of TIMP-1 and TIMP-2 (TIMP-3 is not soluble) have already been investigated in plasma/serum of preeclampsia pregnant compared to healthy pregnant, this comparison about TIMP-4 level is unknown. Importantly, TIMP-4 is expressed mainly in cardiovascular structures, and some studies have demonstrated high levels of TIMP-4 in some cardiovascular disorders, such as dilated cardiomyopathy and atherosclerosis; nevertheless of these evidences its function in cardiovascular biology and pathology is poorly understood. Aims To compare plasma levels of TIMP-4 between preeclampsia (PE) and healthy pregnant (HP) and to compare TIMP-4 values through of gestation periods (1st, 2nd and 3rd trimester) and post-partum in HP ( n = 18). Methods and results TIMP-4 was measured by ELISA. Pregnant were recruited in two different locations: Study 1 from Minas Gerais State (PE = 43 and HP = 36) and Study 2 from Sao Paulo State (PE = 20 and HP = 20). We found elevated plasma TIMP-4 levels in PE compared to HP in both in Study 1 and Study 2 ( P = 0.0046 and P = 0.0007, respectively). In addition, in the Study 2 we performed correlation among TIMP-4 levels and clinical parameters. We found positive correlation with serum liver enzymes (ALT, r = 0.84, P = 0.004; and AST, r = 0.51, P = 0.02) and proteinuria ( r = 0.66, P = 0.01); and negative correlations with newborn weight ( r = −0.45, P = 0.04). Finally, we observed lack of significant differences among gestational age and postpartum periods in HP group. Conclusions PE present elevated levels of circulating TIMP-4 compared to HP and these levels are correlated with clinical parameters of disease. Finacial Support This study was funded by the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), and the Fundacao o de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP-Brazil).