The apolipoprotein(a) component of lipoprotein(a) mediates binding to laminin: Contribution to selective retention of lipoprotein(a) in atherosclerotic lesions

Angela D'Angelo, Diego Geroldi, Mark A. Hancock, Viviana Valtulina, Antonia I. Cornaglia, Craig A. Spencer, Enzo Emanuele, Alberto Calligaro, Marlys L. Koschinsky, Pietro Speziale, Livia Visai

Research output: Contribution to journalArticlepeer-review

Abstract

Lipoprotein(a) [Lp(a)] entrapment by vascular extracellular matrix may be important in atherogenesis. We sought to determine whether laminin, a major component of the basal membrane, may contribute to Lp(a) retention in the arterial wall. First, immunohistochemistry experiments were performed to examine the relative distribution of Lp(a) and laminin in human carotid artery specimens. There was a high degree of co-localization of Lp(a) and laminin in atherosclerotic specimens, but not in non-atherosclerotic sections. We then studied the binding interaction between Lp(a) and laminin in vitro. ELISA experiments showed that native Lp(a) particles and 17K and 12K recombinant apolipoprotein(a) [r-apo(a)] variants interacted strongly with laminin whereas LDL, apoB-100, and the truncated KIV6-P, KIV8-P, and KIV9-P r-apo(a) variants did not. Overall, the ELISA data demonstrated that Lp(a) binding to laminin is mediated by apo(a) and a combination of the lysine analogue ε-aminocaproic acid and salt effectively decreases apo(a) binding to laminin. Secondary binding analyses with 125I-labeled r-apo(a) revealed equilibrium dissociation constants (Kd) of 180 and 360 nM for the 17K and 12K variants binding to laminin, respectively. Such similar Kd values between these two r-apo(a) variants suggest that isoform size does not appear to influence apo(a) binding to laminin. In summary, our data suggest that laminin may bind to apo(a) in the atherosclerotic intima, thus contributing to the selective retention of Lp(a) in this milieu.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1687
Issue number1-3
DOIs
Publication statusPublished - Feb 21 2005

Keywords

  • Apolipoprotein(a)
  • Atherosclerosis
  • Laminin
  • Lipoprotein(a)

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biophysics

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