Apolipoprotein E mediates the retention of high-density lipoproteins by mouse carotid arteries and cultured arterial smooth muscle cell extracellular matrices

Katherine Olin-Lewis, Jeana L. Benton, John C Rutledge, Denis G. Baskin, Thomas N. Wight, Alan Chait

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Lipoprotein retention in the vascular extracellular matrix (ECM) plays a critical role in atherogenesis. Previous studies demonstrated the presence of apo A-I and E in atherosclerotic lesions, suggesting that HDL may be trapped by the artery wall. We sought to determine mechanisms by which HDL could be bound and retained by the arterial wall, and whether apo E was a principal determinant of this binding. We evaluated in situ accumulation of fluorescently labeled DiI-human HDL±apo E in perfused carotid arteries from apo E-null mice. Apo E was important in mediating HDL binding to the vascular wall, with a 48±16% increase in accumulation of DiI-labeled apo E-containing HDL (HDL3+E) compared with DiI-apo E-free HDL (HDL3-E) (P=0.003). To investigate possible mechanisms responsible for retention, we assessed binding of unlabeled HDL3-E and HDL3+E to ECM generated by cultured arterial smooth muscle cells. Similar to the in situ carotid artery data, HDL3+E bound better to the ECM than did HDL3-E (3-fold lower Ka and 3.5-fold higher Bmax for HDL3+E versus HDL3-E). These differences were eliminated after either neutralization of arginine residues on apo E or digestion of matrix with chondroitin ABC lyase, suggesting that chondroitin and/or dermatan sulfate proteoglycans were responsible for apo E-mediated increased binding. These findings demonstrate that HDL can bind to both intact murine carotid arteries and smooth muscle cell-derived ECM, and that apo E is a principal determinant in mediating the ability of HDL to be trapped and retained via its interaction with ECM proteoglycans.

Original languageEnglish (US)
Pages (from-to)1333-1339
Number of pages7
JournalCirculation Research
Volume90
Issue number12
DOIs
StatePublished - Jun 28 2002
Externally publishedYes

Keywords

  • Apolipoprotein E
  • Artery wall
  • Extracellular matrix
  • High-density lipoproteins
  • Proteoglycan

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Apolipoprotein E mediates the retention of high-density lipoproteins by mouse carotid arteries and cultured arterial smooth muscle cell extracellular matrices'. Together they form a unique fingerprint.

  • Cite this