title: 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.
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.
authors.affiliation: Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695 011, India.
authors.forename: Vasantha
authors.initials: V
authors.lastname: Kalaivani
authors.forename: Padinjaradath Sankunni
authors.initials: PS
authors.lastname: Appukuttan
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001054:Apolipoproteins A / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004705:Endocytosis; D005347:Fibroblasts / Q000378:metabolism; D037483:Galectin 1 / Q000097:blood / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D017270:Lipoprotein(a) / Q000097:blood / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000378:metabolism; D055815:Young Adult
chemical_list: D001054:Apolipoproteins A; D037483:Galectin 1; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D046912:Multiprotein Complexes; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein