Cholesterol loading of macrophages leads to marked enhancement of native lipoprotein(a) and apoprotein(a) internalization and degradation
Lipoprotein(a) levels in the plasma are strongly correlated with atherosclerotic coronary artery disease. Although the mechanism of this effect is not known, the interaction of lipoprotein(a) with macrophages may be important. Previous work has shown that macrophages in culture internalize and degra...
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Veröffentlicht in: | The Journal of biological chemistry 1993-04, Vol.268 (12), p.8569-8573 |
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Sprache: | eng |
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Zusammenfassung: | Lipoprotein(a) levels in the plasma are strongly correlated with atherosclerotic coronary artery disease. Although the mechanism
of this effect is not known, the interaction of lipoprotein(a) with macrophages may be important. Previous work has shown
that macrophages in culture internalize and degrade native lipoprotein(a) poorly. In the present study, the interaction of
Lp(a) with mouse peritoneal and human monocyte-derived macrophages that were cholesterol-loaded, such as occur in atheromata,
was investigated. 125I-Lp(a) degradation was increased 4-5-fold in macrophages that had been loaded with cholesterol by incubation
with acetyl-LDL for 2-4 days. The enhanced degradation of Lp(a) by foam cells was chloroquine-sensitive and dependent upon
the presence of calcium in the extracellular medium. Incubation of the macrophages with acetyl-LDL plus an inhibitor of acyl
CoA:cholesterol acyltransferase, which increased the free cholesterol content and decreased the cholesteryl ester content
of the cells, resulted in an even greater up-regulation of 125I-Lp(a) degradation (8-23-fold over control macrophages). The
interaction of Lp(a) with cholesterol-loaded macrophages involved the apoprotein(a) moiety of Lp(a) since 125I-apoprotein(a),
but not 125I-Lp(a-), was degraded to a much greater extent by foam cells compared to control macrophages. The uptake and degradation
of Lp(a) in foam cells was not mediated by LDL, scavenger, LDL receptor-related protein (LRP), or plasminogen receptors. Thus,
cholesterol loading of macrophages markedly enhances the internalization and lysosomal degradation of Lp(a) and apo(a) by
a calcium-dependent receptor activity different from known lipoprotein receptors. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(18)52913-6 |