TY - JOUR
T1 - Calcification in human intracranial aneurysms is highly prevalent and displays both atherosclerotic and nonatherosclerotic types
AU - Gade, Piyusha S.
AU - Tulamo, Riikka
AU - Lee, Kee Won
AU - Mut, Fernando
AU - Ollikainen, Eliisa
AU - Chuang, Chih Yuan
AU - Jae Chung, Bong
AU - Niemelä, Mika
AU - Rezai Jahromi, Behnam
AU - Aziz, Khaled
AU - Yu, Alexander
AU - Charbel, Fady T.
AU - Amin-Hanjani, Sepideh
AU - Frösen, Juhana
AU - Cebral, Juan R.
AU - Robertson, Anne M.
N1 - Publisher Copyright:
© 2019 American Heart Association, Inc.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Objective: Although the clinical and biological importance of calcification is well recognized for the extracerebral vasculature, its role in cerebral vascular disease, particularly, intracranial aneurysms (IAs), remains poorly understood. Extracerebrally, 2 distinct mechanisms drive calcification, a nonatherosclerotic, rapid mineralization in the media and a slower, inflammation driven, atherosclerotic mechanism in the intima. This study aims to determine the prevalence, distribution, and type (atherosclerotic, nonatherosclerotic) of calcification in IAs and assess differences in occurrence between ruptured and unruptured IAs. Approach and Results: Sixty-five 65 IA specimens (48 unruptured, 17 ruptured) were resected perioperatively. Calcification and lipid pools were analyzed nondestructively in intact samples using high resolution (0.35 μm) microcomputed tomography. Calcification is highly prevalent (78%) appearing as micro (<500 μm), meso (500 μm-1 mm), and macro (>1 mm) calcifications. Calcification manifests in IAs as both nonatherosclerotic (calcification distinct from lipid pools) and atherosclerotic (calcification in the presence of lipid pools) with 3 wall types: Type I - only calcification, no lipid pools (20/51, 39%), Type II - calcification and lipid pools, not colocalized (19/51, 37%), Type III - calcification colocalized with lipid pools (12/51, 24%). Ruptured IAs either had no calcifications or had nonatherosclerotic micro- or meso-calcifications (Type I or II), without macro-calcifications. Conclusions: Calcification in IAs is substantially more prevalent than previously reported and presents as both nonatherosclerotic and atherosclerotic types. Notably, ruptured aneurysms had only nonatherosclerotic calcification, had significantly lower calcification fraction, and did not contain macrocalcifications. Improved understanding of the role of calcification in IA pathology should lead to new therapeutic targets.
AB - Objective: Although the clinical and biological importance of calcification is well recognized for the extracerebral vasculature, its role in cerebral vascular disease, particularly, intracranial aneurysms (IAs), remains poorly understood. Extracerebrally, 2 distinct mechanisms drive calcification, a nonatherosclerotic, rapid mineralization in the media and a slower, inflammation driven, atherosclerotic mechanism in the intima. This study aims to determine the prevalence, distribution, and type (atherosclerotic, nonatherosclerotic) of calcification in IAs and assess differences in occurrence between ruptured and unruptured IAs. Approach and Results: Sixty-five 65 IA specimens (48 unruptured, 17 ruptured) were resected perioperatively. Calcification and lipid pools were analyzed nondestructively in intact samples using high resolution (0.35 μm) microcomputed tomography. Calcification is highly prevalent (78%) appearing as micro (<500 μm), meso (500 μm-1 mm), and macro (>1 mm) calcifications. Calcification manifests in IAs as both nonatherosclerotic (calcification distinct from lipid pools) and atherosclerotic (calcification in the presence of lipid pools) with 3 wall types: Type I - only calcification, no lipid pools (20/51, 39%), Type II - calcification and lipid pools, not colocalized (19/51, 37%), Type III - calcification colocalized with lipid pools (12/51, 24%). Ruptured IAs either had no calcifications or had nonatherosclerotic micro- or meso-calcifications (Type I or II), without macro-calcifications. Conclusions: Calcification in IAs is substantially more prevalent than previously reported and presents as both nonatherosclerotic and atherosclerotic types. Notably, ruptured aneurysms had only nonatherosclerotic calcification, had significantly lower calcification fraction, and did not contain macrocalcifications. Improved understanding of the role of calcification in IA pathology should lead to new therapeutic targets.
KW - Aneurysm, ruptured
KW - Calcification
KW - Intracranial aneurysms
KW - Lipid
KW - Prevalence
UR - http://www.scopus.com/inward/record.url?scp=85072687128&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.119.312922
DO - 10.1161/ATVBAHA.119.312922
M3 - Article
C2 - 31462093
AN - SCOPUS:85072687128
SN - 1079-5642
VL - 39
SP - 2157
EP - 2167
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 10
ER -