STUDIES ON EFFECTS OF LP(A) LIPOPROTEIN ON GENE-EXPRESSION IN ENDOTHELIAL-CELLS IN-VITRO

The reason(s) for the atherogenic properties of Lp(a) lipoprotein is s till unclear, and several mechanisms have been studied, Alterations in gene expression in endothelial cells (ECs) could be important with re spect to risk for coronary heart disease (CHD). We have tested the eff ects of Lp(a) lipoprotein or the apolipoprotein of Lp(a) lipoprotein ( apo(a)) on cultured human umbilical vein endothelial cells (HUVECs) wi th respect to: (1) the level of endothelin-1 (ET-1) mRNA; (2) release of ET-1 into the culture medium, (3) plasminogen activator inhibitor-1 (PAI-1) secretion into the culture medium and; (4) total gene express ion in HUVECs, examined by a polymerase chain reaction (PCR)-based tec hnique, differential display-reverse transcription-PCR (DD-RT-PCR), Lp (a) lipoprotein reduced the level of ET-1 mRNA as well as the release of ET-1. The reduction of ET-1 in the medium was even more pronounced when HUVECs were incubated with apo(a), but we found no effect of apo( a) on ET-1 mRNA level. Neither Lp(a) lipoprotein nor apo(a) had a sign ificant influence on PAI-1 secretion, DD-RT-PCR revealed 11 fragments that could represent differences between cells exposed or not exposed to Lp(a) lipoprotein, Following subcloning and sequencing, 18 sequence s that differed between exposed and unexposed cultures were obtained, Four of the subcloned fragments have up to now been used as a probe fo r northern blot analyses, and one fragment was confirmed to be regulat ed by Lp(a) lipoprotein. In conclusion, Lp(a) lipoprotein is shown to control ET-1 mRNA levels and the function of at least one more gene, t he nature of which is unknown.