Smooth Muscle Cell Foam Cell Formation, Apolipoproteins, and ABCA1 in Intracranial Aneurysms: Implications for Lipid Accumulation as a Promoter of Aneurysm Wall Rupture

J Neuropathol Exp Neurol. 2016 Jul;75(7):689-99. doi: 10.1093/jnen/nlw041. Epub 2016 Jun 9.


Saccular intracranial aneurysm (sIA) aneurysm causes intracranial hemorrhages that are associated with high mortality. Lipid accumulation and chronic inflammation occur in the sIA wall. A major mechanism for lipid clearance from arteries is adenosine triphosphate-binding cassette A1 (ABCA1)-mediated lipid efflux from foam cells to apolipoprotein A-I (apoA-I). We investigated the association of wall degeneration, inflammation, and lipid-related parameters in tissue samples of 16 unruptured and 20 ruptured sIAs using histology and immunohistochemistry. Intracellular lipid accumulation was associated with wall remodeling (p = 0.005) and rupture (p = 0.020). Foam cell formation was observed in smooth muscle cells, in addition to CD68- and CD163-positive macrophages. Macrophage infiltration correlated with intracellular lipid accumulation and apolipoproteins, including apoA-I. ApoA-I correlated with markers of lipid accumulation and wall degeneration (p = 0.01). ApoA-I-positive staining colocalized with ABCA1-positive cells particularly in sIAs with high number of smooth muscle cells (p = 0.003); absence of such colocalization was associated with wall degeneration (p = 0.017). Known clinical risk factors for sIA rupture correlated inversely with apoA-I. We conclude that lipid accumulation associates with sIA wall degeneration and risk of rupture, possibly via formation of foam cells and subsequent loss of mural cells. Reduced removal of lipids from the sIA wall via ABCA1-apoA-I pathway may contribute to this process.

Keywords: Apolipoproteins; Atherosclerosis; Inflammation; Intracranial Aneurysm; Lipid; Smooth Muscle Cell..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Aneurysm, Ruptured / metabolism*
  • Aneurysm, Ruptured / pathology
  • Apolipoprotein A-I / metabolism*
  • Foam Cells / metabolism*
  • Foam Cells / pathology
  • Humans
  • Intracranial Aneurysm / metabolism*
  • Intracranial Aneurysm / pathology
  • Lipid Accumulation Product / physiology*
  • Middle Aged
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology


  • ABCA1 protein, human
  • APOA1 protein, human
  • ATP Binding Cassette Transporter 1
  • Apolipoprotein A-I