Lipoprotein (a) downregulates lysosomal acid lipase and induces interleukin-6 in human blood monocytes.
The association of elevated lipoprotein (a) (Lp(a)) with an increased risk for coronary events is clearly established. This increased risk may in part be due to the activation of monocytes as major cells involved in atherogenesis. High concentrations of plasma Lp(a) were shown to influence the gene expression of human blood monocytes and in the present study we demonstrate a reduced abundance of the lysosomal acid lipase (LAL) mRNA in monocytes of patients with coronary disease and selective Lp(a) hyperlipidemia. This is also supported by in vitro studies where purified Lp(a) but not low-density lipoprotein (LDL) was shown to downregulate mRNA levels of the LAL in control monocytes. A correlation of Lp(a) serum levels and the proinflammatory cytokine IL-6 was recently also described. Therefore, we investigated whether Lp(a) is capable to enhance the release of this acute phase cytokine from human blood monocytes. Purified Lp(a) led to an increased secretion of IL-6, but not TNF-alpha arguing against a general activation of these cells. The association of reduced LAL activity with the premature development of coronary artery disease has been demonstrated in patients with hypercholesterolemia, and in the present study we show for the first time that LAL expression is suppressed in monocytes from patients with Lp(a) hyperlipidemia and by purified Lp(a). In addition, increased levels of IL-6 also predict future cardiovascular events and IL-6 secretion was also induced by purified Lp(a).
Buechler
Christa
C
Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Straubeta Allee 11, D-93042 Regensburg, Germany.
Ullrich
Heidrun
H
Aslanidis
Charalampos
C
Bared
Salim Maa
SM
Lingenhel
Arno
A
Ritter
Mirko
M
Schmitz
Gerd
G
D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D006949:Hyperlipidemias / Q000201:enzymology / Q000235:genetics; D015850:Interleukin-6 / Q000378:metabolism*; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D017270:Lipoprotein(a) / Q000378:metabolism* / Q000494:pharmacology; D008247:Lysosomes / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D017270:Lipoprotein(a); D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D008049:Lipase