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Interaction of a recombinant form of apolipoprotein[a] with human fibroblasts and with the human hepatoma cell line HepG2
Abstract
We have studied the binding, uptake, and degradation of a recombinant form of apolipoprotein[a] (r-apo[a]) using a cultured cell model. In HepG2 cells and in human fibroblasts, r-apo[a] complexed with low density lipoprotein(LDL) is bound and internalized via high affinity (Kd = 10 nM) receptors; in both cell types, low affinity (Kd = 200-300 nM) sites also mediate free apo[a] uptake. Using competition studies, we found that the high affinity binding component corresponds to the LDL receptor. Involvement of the LDL receptor in r-apo[a] uptake by fibroblasts was confirmed using fibroblasts derived from an individual homozygous for familial hypercholesterolemia; in contrast to normal fibroblasts, these cells lacked the high affinity r-apo[a] binding component. Cell association of 125I-labeled r-apo[a] was increased and decreased concomitantly with the up- and down-regulation of the LDL receptor in response to a number of compounds. The addition of alpha 2-macroglobulin as well as treatment with heparinase, chondroitinase ABC, and sodium chlorate did not decrease total specific binding of r-apo[a], suggesting that neither the low density lipoprotein receptor-related protein nor cell surface proteoglycans are involved in r-apo[a] clearance. The low affinity binding component present in both fibroblasts and HepG2 cells likely corresponds to the plasminogen receptor, as binding of r-apo[a] to these sites was specifically decreased by the addition of plasminogen or the lysine analog…
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Multiple studies of LDLR in cells, animal models, and humans have provided inconsistent or conflicting results.
“Multiple studies of the LDL receptor (LDLR) in cells27-34, animal models25,32,35,36, and humans10,28,37-48 have provided inconsistent or conflicting results.”
From Functional interrogation of cellular Lp(a) uptake by genome-scale CRISPR screening (2025) · cites this paper as [29]
Multiple studies in cells have provided support for an interaction between Lp(a) and LDLR.
“Indeed, multiple studies in cells have provided support for an interaction between Lp(a) and LDLR27-30.”
From Functional interrogation of cellular Lp(a) uptake by genome-scale CRISPR screening (2025) · cites this paper as [29]
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cDNA sequence of human apolipoprotein(a) is homologous to plasminogen
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Functional interrogation of cellular Lp(a) uptake by genome-scale CRISPR screening
Khan, T. G., Bragazzi Cunha, J., Raut, C., Burroughs, M., Vyas, H. S., Leix, K., Goonewardena, S. N., Smrcka, A. V., Speliotes, E. K., & Emmer, B. T. (2025) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2025.119174 · Cited by 6
Metadata
- Authors
- Tam, S. P., Zhang, X., & Koschinsky, M. L.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 1996-03
- Volume
- 37
- Issue
- 3
- Pages
- 518-533
- ISSN
- 0022-2275
- Cited by
- 44
- References
- 1
- Language
- en
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