Ke. Berge et al., STUDIES ON EFFECTS OF LP(A) LIPOPROTEIN ON GENE-EXPRESSION IN ENDOTHELIAL-CELLS IN-VITRO, Clinical genetics, 52(5), 1997, pp. 314-325
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.