title: Lipid accumulation, lipid oxidation, and low plasma levels of acquired antibodies against oxidized lipids associate with degeneration and rupture of the intracranial aneurysm wall.
abstract: BACKGROUND
  Rupture of a saccular intracranial aneurysm (sIA) causes an often fatal subarachnoid hemorrhage (SAH). Why some sIAs rupture remains unknown. Since sIA walls bear some histological similarities with early atherosclerotic lesions, we hypothesized that accumulation and oxidation of lipids might occur in the sIA wall and might associate with sIA wall degeneration. Tissue samples from sIA fundi (n = 54) were studied with histochemistry and a panel of previously characterized antibodies for epitopes of oxidized LDL (OxLDL). Plasma samples from sIA carriers (n = 125) were studied with ELISA and EIA for IgG and IgM -antibodies against a panel of OxLDL epitopes.
  
  
  RESULTS
  Lipid accumulation, foam cells, and oxidized lipids were found both in unruptured and ruptured sIA walls. Lipid accumulation associated with wall degeneration (P < 0.001), as did the expression of adipophilin, a marker of lipid ingestion by cells. Lipid accumulation associated also with loss of mural cells (P < 0.001), as did the accumulation of OxLDL (P < 0.001). Plasma IgG antibody titers against OxLDL or malondialdehyde modified LDL were higher in patients with unruptured sIAs than in patients with aneurysmal SAH (P ≤ 0.001). A trend but not statistically significant differences were found in plasma IgM antibodies against oxidized lipids.
  
  
  CONCLUSIONS
  Accumulation of lipids and their oxidation in the sIA wall associates with the degeneration of the sIA wall. Acquired immunity against oxidized lipid epitopes may be protective of lipid associated sIA wall degeneration, but warrants further studies.
authors.affiliation: Neurosurgery Research Group, Neuroscience program, Biomedicum Helsinki, Biomedicum, Helsinki, Finland. juhana.frosen@hus.fi.
authors.forename: Juhana
authors.initials: J
authors.lastname: Frösen
authors.forename: Riikka
authors.initials: R
authors.lastname: Tulamo
authors.forename: Tommi
authors.initials: T
authors.lastname: Heikura
authors.forename: Sini
authors.initials: S
authors.lastname: Sammalkorpi
authors.forename: Mika
authors.initials: M
authors.lastname: Niemelä
authors.forename: Juha
authors.initials: J
authors.lastname: Hernesniemi
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Levonen
authors.forename: Sohvi
authors.initials: S
authors.lastname: Hörkkö
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017542:Aneurysm, Ruptured / Q000378:metabolism* / Q000473:pathology; D000906:Antibodies / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D002532:Intracranial Aneurysm / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction; D000070780:Perilipin-2
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070780:Perilipin-2; D008315:Malondialdehyde