Smooth Muscle Cell Foam Cell Formation, Apolipoproteins, and ABCA1 in Intracranial Aneurysms: Implications for Lipid Accumulation as a Promoter of Aneurysm Wall Rupture.
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.
From the Biomedicum, Neurosurgery Research Group, Helsinki, Finland (EO, RT, JH, MN, JF); Biomedicum, Wihuri Research Institute, Helsinki, Finland (EO, SL, ML-R, PTK); Department of Vascular Surgery, Helsinki University Central Hospital, Helsinki, Finland (RT); Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland (JH, MN); Department of Molecular Medicine, AIV-Institute, Kuopio, Finland, University of Eastern Finland (SY-H); Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland (JF); and Hemorrhagic Brain Pathology Research Group, Kuopio University Hospital, Kuopio, Finland (JF).
Eliisa
E
Ollikainen
From the Biomedicum, Neurosurgery Research Group, Helsinki, Finland (EO, RT, JH, MN, JF); Biomedicum, Wihuri Research Institute, Helsinki, Finland (EO, SL, ML-R, PTK); Department of Vascular Surgery, Helsinki University Central Hospital, Helsinki, Finland (RT); Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland (JH, MN); Department of Molecular Medicine, AIV-Institute, Kuopio, Finland, University of Eastern Finland (SY-H); Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland (JF); and Hemorrhagic Brain Pathology Research Group, Kuopio University Hospital, Kuopio, Finland (JF).
Riikka
R
Tulamo
From the Biomedicum, Neurosurgery Research Group, Helsinki, Finland (EO, RT, JH, MN, JF); Biomedicum, Wihuri Research Institute, Helsinki, Finland (EO, SL, ML-R, PTK); Department of Vascular Surgery, Helsinki University Central Hospital, Helsinki, Finland (RT); Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland (JH, MN); Department of Molecular Medicine, AIV-Institute, Kuopio, Finland, University of Eastern Finland (SY-H); Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland (JF); and Hemorrhagic Brain Pathology Research Group, Kuopio University Hospital, Kuopio, Finland (JF).
Satu
S
Lehti
From the Biomedicum, Neurosurgery Research Group, Helsinki, Finland (EO, RT, JH, MN, JF); Biomedicum, Wihuri Research Institute, Helsinki, Finland (EO, SL, ML-R, PTK); Department of Vascular Surgery, Helsinki University Central Hospital, Helsinki, Finland (RT); Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland (JH, MN); Department of Molecular Medicine, AIV-Institute, Kuopio, Finland, University of Eastern Finland (SY-H); Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland (JF); and Hemorrhagic Brain Pathology Research Group, Kuopio University Hospital, Kuopio, Finland (JF).
Miriam
M
Lee-Rueckert
From the Biomedicum, Neurosurgery Research Group, Helsinki, Finland (EO, RT, JH, MN, JF); Biomedicum, Wihuri Research Institute, Helsinki, Finland (EO, SL, ML-R, PTK); Department of Vascular Surgery, Helsinki University Central Hospital, Helsinki, Finland (RT); Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland (JH, MN); Department of Molecular Medicine, AIV-Institute, Kuopio, Finland, University of Eastern Finland (SY-H); Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland (JF); and Hemorrhagic Brain Pathology Research Group, Kuopio University Hospital, Kuopio, Finland (JF).
Juha
J
Hernesniemi
From the Biomedicum, Neurosurgery Research Group, Helsinki, Finland (EO, RT, JH, MN, JF); Biomedicum, Wihuri Research Institute, Helsinki, Finland (EO, SL, ML-R, PTK); Department of Vascular Surgery, Helsinki University Central Hospital, Helsinki, Finland (RT); Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland (JH, MN); Department of Molecular Medicine, AIV-Institute, Kuopio, Finland, University of Eastern Finland (SY-H); Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland (JF); and Hemorrhagic Brain Pathology Research Group, Kuopio University Hospital, Kuopio, Finland (JF).
Mika
M
Niemelä
From the Biomedicum, Neurosurgery Research Group, Helsinki, Finland (EO, RT, JH, MN, JF); Biomedicum, Wihuri Research Institute, Helsinki, Finland (EO, SL, ML-R, PTK); Department of Vascular Surgery, Helsinki University Central Hospital, Helsinki, Finland (RT); Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland (JH, MN); Department of Molecular Medicine, AIV-Institute, Kuopio, Finland, University of Eastern Finland (SY-H); Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland (JF); and Hemorrhagic Brain Pathology Research Group, Kuopio University Hospital, Kuopio, Finland (JF).
Seppo
S
Ylä-Herttuala
From the Biomedicum, Neurosurgery Research Group, Helsinki, Finland (EO, RT, JH, MN, JF); Biomedicum, Wihuri Research Institute, Helsinki, Finland (EO, SL, ML-R, PTK); Department of Vascular Surgery, Helsinki University Central Hospital, Helsinki, Finland (RT); Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland (JH, MN); Department of Molecular Medicine, AIV-Institute, Kuopio, Finland, University of Eastern Finland (SY-H); Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland (JF); and Hemorrhagic Brain Pathology Research Group, Kuopio University Hospital, Kuopio, Finland (JF).
Petri T
PT
Kovanen
From the Biomedicum, Neurosurgery Research Group, Helsinki, Finland (EO, RT, JH, MN, JF); Biomedicum, Wihuri Research Institute, Helsinki, Finland (EO, SL, ML-R, PTK); Department of Vascular Surgery, Helsinki University Central Hospital, Helsinki, Finland (RT); Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland (JH, MN); Department of Molecular Medicine, AIV-Institute, Kuopio, Finland, University of Eastern Finland (SY-H); Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland (JF); and Hemorrhagic Brain Pathology Research Group, Kuopio University Hospital, Kuopio, Finland (JF) juhana.frosen@kuh.fi.
Juhana
J
Frösen
D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017542:Aneurysm, Ruptured / Q000378:metabolism* / Q000473:pathology; D016632:Apolipoprotein A-I / Q000378:metabolism*; D005487:Foam Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D002532:Intracranial Aneurysm / Q000378:metabolism* / Q000473:pathology; D064237:Lipid Accumulation Product / Q000502:physiology*; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology
C577836:ABCA1 protein, human; C505693:APOA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I
Apolipoproteins; Atherosclerosis; Inflammation; Intracranial Aneurysm; Lipid; Smooth Muscle Cell.