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Circulating Lp(a):LDL Complexes Contain LDL Molecules Proportionate to Lp(a) Size and Bind to Galectin-1: A Possible Route for LDL Entry into Cells

  • Original Article
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Lipids

Abstract

The molecular mechanism of vascular pathology mediated by circulating lipoprotein(a) [Lp(a)] remains unknown. We examined the role of two distinguishing features of Lp(a) viz non-covalent complex formation with a low density lipoprotein (LDL) and heavy glycosylation as determinants of binding of this lipoprotein and its LDL complex to cell-surface receptors. LDL isolated from the Lp(a):LDL complex, free LDL and oxidized LDL were equally efficient in forming a reconstituted complex with pure Lp(a). Complexed LDL in healthy individuals was equal in oxidation status to free LDL. The number of LDL molecules associated with each Lp(a) molecule (LDL index) in plasma samples increased steadily with Lp(a) size (correlation coefficient r = 0.834). Complex reconstituted from purified plasma Lp(a) and LDL maintained the same LDL index as plasma in accordance with Lp(a) size. Consequently, the percentage of complex-free Lp(a) in the plasma decreased sharply with Lp(a) size (r = −0.887). Although O-glycosylation measured in terms of lectin binding increased with Lp(a) size, the LDL index increased significantly faster than O-glycosylation among Lp(a) phenotypes of different plasma samples. Complexes with varying stoichiometry existed in the same plasma. Extra LDL complex molecules were not recognized by LDL receptors on human macrophages or rat cardiac fibroblasts indicating attachment to Lp(a) involved LDL receptor-binding sites. However, unlike free LDL complex LDL could attach through Lp(a) to immobilized form of galectin-1, a lectin ubiquitous on mammalian cells. Results suggest that phenotype-dependence of the physiological and pathological functions of Lp(a) may operate through differential LDL-carrier activity.

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Abbreviations

FITC:

Fluorescein isothiocyanate

JL1:

Lipid fraction of jacalin precipitate of plasma

JSL1:

Lipid layer of supernatant after jacalin precipitation of plasma

PBS:

20 mM potassium phosphate buffer with150 mM NaCl, pH 7.4

PBS-T:

PBS containing 0.05 % Tween 20

PEG-6000:

Polyethylene glycol-6000

SDS-PAGE:

Sodium dodecyl sulphate-polyacrylamide gel electrophoresis

TBE:

Tris Borate EDTA buffer (0.05 M Tris, 0.025 M boric acid, 0.003 M disodium salt of EDTA), pH 8.7

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Acknowledgments

The authors are grateful to Dr. Jaisy Mathai, Head, Department of Transfusion Medicine and Dr. Sivakumar, Scientist, Department of Cellular and Molecular Cardiology of this institute for provision of out-dated plasma samples and cultured (75 % confluent P3 passage) rat cardiac fibroblasts, respectively. V. Kalaivani received a fellowship from University Grants Commission (UGC), New Delhi, India.

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Authors and Affiliations

  1. Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695 011, India

    Vasantha Kalaivani & Padinjaradath Sankunni Appukuttan

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  1. Vasantha Kalaivani
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  2. Padinjaradath Sankunni Appukuttan
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Correspondence to Padinjaradath Sankunni Appukuttan.

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Kalaivani, V., Appukuttan, P.S. Circulating Lp(a):LDL Complexes Contain LDL Molecules Proportionate to Lp(a) Size and Bind to Galectin-1: A Possible Route for LDL Entry into Cells. Lipids 49, 1101–1113 (2014). https://doi.org/10.1007/s11745-014-3941-4

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  • DOI: https://doi.org/10.1007/s11745-014-3941-4

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