Pre-eclampsia-induced alterations in IGF-I of human umbilical cord

BACKGROUND: Extracellular matrix (ECM)-components serve as a storage site to concentrate and stabilise growth factors in the vicinity of cells. Human umbilical cord (UC) tissues contain significant amounts of IGF-I and IGF-binding proteins (BPs). IGF-I is known as a stimulator of collagen and sulphated glycosaminoglycans (GAGs) biosynthesis. Pre-eclampsia, the most common pregnancy associated syndrome, is accompanied by an accumulation of collagen and sulphated glycosaminoglycans in the UC. One may expect that IGF-I and BPs play an important role in such a remodelling of the UC tissue. For this reason it was decided to evaluate the alterations in amounts of IGF-I and BPs in UC serum and in the UC arterial wall of newborns delivered by mothers with pre-eclampsia. MATERIALS AND METHODS: Studies were performed on the UCs of 12 control and 12 investigated newborns, delivered by mothers with pre-eclampsia (edema, proteinuria > 500 mg l-1, arterial pressure: systolic > 140 mmHg, diastolic > 100 mmHg). Radioimmunological techniques were employed to determine IGF-I and IGF-BPs (BP-1 and BP-3). RESULTS: It was found that pre-eclampsia is associated with an increase of IGF-I concentration in the UC serum and with simultaneous decrease of its content in the umbilical cord artery (UCA). The decrease of IGF-I content in the UCA wall was accompanied by an increase of BP-3 and BP-1 in this tissue. The increase in BPs content in the UCA wall was not associated with an enhancement of IGF binding by extracts from the homogenates of arterial wall. Heparin drastically decreased the binding of IGF-I by BP-3. CONCLUSIONS: Pre-eclampsia is associated with an increase of IGF-I-concentration in the umbilical cord blood and an elevation of BPs contents in the UCA wall. Despite a high concentration of binding proteins, IGF-I is not accumulated in this tissue. High amounts of sulphated GAGs in the UCA wall may be a factor that prevents the binding of IGF-I by BPs. Free IGF-I can easily bind to cell receptors and stimulate the cells to produce collagen and sulphated GAGs in the arterial wall.