Dataset Information

Calcification in Human Intracranial Aneurysms Is Highly Prevalent and Displays Both Atherosclerotic and Nonatherosclerotic Types.

ABSTRACT: 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 ?m) 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.

SUBMITTER: Gade PS

PROVIDER: S-EPMC6911659 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Calcification in Human Intracranial Aneurysms Is Highly Prevalent and Displays Both Atherosclerotic and Nonatherosclerotic Types.

Gade Piyusha S PS Tulamo Riikka R Lee Kee-Won KW Mut Fernando F Ollikainen Eliisa E Chuang Chih-Yuan CY Jae Chung Bong B Niemelä Mika M Rezai Jahromi Behnam B Aziz Khaled K Yu Alexander A Charbel Fady T FT Amin-Hanjani Sepideh S Frösen Juhana J Cebral Juan R JR Robertson Anne M AM

Arteriosclerosis, thrombosis, and vascular biology 20190829 10

<h4>Objective</h4>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, an ...[more]

PMID: 31462093

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Project description:Intracranial aneurysms are pathological dilatations of the cerebral artery, while rupture of intracranial aneurysms causes life-threatening subarachnoid hemorrhage. The molecular mechanisms of pathogenesis of intracranial aneurysms are poorly understood. MicroRNAs have fundamental roles in modulating vascular biology and disease. In the present study, we carried out a genome-wide characterization on expressions of microRNAs, and performed integrative analyses in conjunction with changes of the transcriptome in human intracranial aneurysms.Genome-wide microRNA screening was performed in 6 intracranial aneurysmal samples and 6 normal superficial temporal arteries. Each case and control pair was individually matched with gender, age (±5 years), and high blood pressure history. Microarray analysis was performed using Agilent Human miRNA arrays.As compared to normal arteries, we identified 157 microRNAs that were differentially expressed in the aneurysmal tissue (P?<?0.05 and fold change???2), including 72 upregulated and 85 downregulated. The changed microRNAs included endothelium-enriched microRNAs such as members of the let-7 family, miR-17, miR-23b, miR-126, hsa-miR-24-1 and miR-222, and vascular smooth muscle-enriched miRNAs such as miR-143 and miR-145. Moreover, miR-1, miR-10a, miR-125b, and miR-26a, which were implicated in modulating vascular smooth muscle cell functions such as proliferation, apoptosis and shift of phenotype, were also changed. In contrast, microRNAs involved in monocyte and macrophage functions, such as miR-155, miR-146a, miR-223, and miR-124a, were not significantly changed. Bioinformatic analysis revealed that the changed microRNAs were associated with several biological processes related to aneurysm formation, including inflammation, dysregulation of extracellular matrix, smooth muscle cell proliferation, programmed cell death, and response to oxidative stress. Interestingly, we found that a subset of the potential microRNA target genes belonged to the protein translation machinery, including various eukaryotic translation initiation factors and ribosomal proteins, and this finding was highly correlated with our previous transcriptome data showing that multiple genes of the ribosomal proteins and translation initiation and elongation factors were significantly downregulated in human intracranial aneurysms.Our results support that dysregulated microRNAs may have a pathogenic role in intracranial aneurysms. Disruption of the protein translation process may have a pathogenic role in the development of intracranial aneurysms.

Dataset Information

Calcification in Human Intracranial Aneurysms Is Highly Prevalent and Displays Both Atherosclerotic and Nonatherosclerotic Types.

Publications

Calcification in Human Intracranial Aneurysms Is Highly Prevalent and Displays Both Atherosclerotic and Nonatherosclerotic Types.

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