Increase in matrix metalloproteinases from endothelial cells exposed to umbilical cord plasma from high birth weight newborns

Abstract

Large for gestational age infants have increased risk of developing the metabolic syndrome and cardiovascular disease in child- and adulthood. The vascular endothelium is a target site in the pathogenesis of many cardiovascular disorders. The matrix metalloproteinases (MMP) are important modulators of the extracellular matrix and serve as markers of these disorders. Here, we asked whether umbilical cord plasma of high birth weight (HBW; >4 kg) infants could modulate functional properties of human umbilical vein endothelial cells (HUVEC) compared with plasma from normal birth weight (NBW; 3.1-3.6 kg) infants. To test this, HUVECs were exposed for 48 h to 20% venous cord plasma from HBW or NBW infants. The MMP activity in supernatants of HUVECs exposed to HBW plasma was nearly three times higher (P < 0.05) than that obtained with NBW plasma. MMP-9, but not MMP-2, protein concentration and mRNA expression were enhanced in HBW (P < 0.05). With specific blockers, MMP activity and mRNA-MMP-9 were inhibited by approximately 60-70%. Cord lipid and insulin concentrations were similar (P > 0.05) among the two groups. We could not detect any significant differences between the two groups in the concentrations of proinflammatory cytokines or specific tissue inhibitors of MMP in plasma or HUVEC supernatants. In conclusion, cord plasma from HBW infants induced more MMP-9 in HUVECs compared with cord plasma from NBW infants. Although not identified, cord plasma of HBW infants may contain factors that increase endothelial cell MMP. These findings may indicate an association between fetal nutritional conditions and endothelial cell functions.