Dataset Information

Impact of Fiber Structure on the Material Stability and Rupture Mechanisms of Coronary Atherosclerotic Plaques.

ABSTRACT: The rupture of an atherosclerotic plaque in the coronary circulation remains the main cause of heart attack. As a fiber-oriented structure, the fiber structure, in particular in the fibrous cap (FC), may affect both loading and material strength in the plaque. However, the role of fiber orientation and dispersion in plaque rupture is unclear. Local orientation and dispersion of fibers were calculated for the shoulder regions, mid FC, and regions with intimal thickening (IT) from histological images of 16 human coronary atherosclerotic lesions. Finite element analysis was performed to assess the effect of these properties on mechanical conditions. Fibers in shoulder regions had markedly reduced alignment (Median [interquartile range] 12.9° [6.6, 18.0], p < 0.05) compared with those in mid FC (6.1° [5.5, 9.0]) and IT regions (6.7° [5.1, 8.6]). Fiber dispersion was highest in shoulders (0.150 [0.121, 0.192]), intermediate in IT (0.119 [0.103, 0.144]), and lowest in mid FC regions (0.093 [0.081, 0.105], p < 0.05). When anisotropic properties were considered, stresses were significantly higher for the mid FC (p = 0.030) and IT regions (p = 0.002) and no difference was found for the shoulder or global regions. Shear (sliding) stress between fibers in each region and their proportion of maximum principal stress were: shoulder (25.8 kPa [17.1, 41.2], 12.4%), mid FC (13.9 kPa [5.8, 29.6], 13.8%), and IT (36.5 kPa [25.9, 47.3], 15.5%). Fiber structure within the FC has a marked effect on principal stresses, resulting in considerable shear stress between fibers. Fiber structure including orientation and dispersion may determine mechanical strength and thus rupture of atherosclerotic plaques.

SUBMITTER: Douglas GR

PROVIDER: S-EPMC5415591 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Impact of Fiber Structure on the Material Stability and Rupture Mechanisms of Coronary Atherosclerotic Plaques.

Douglas Graeham R GR Brown Adam J AJ Gillard Jonathan H JH Bennett Martin R MR Sutcliffe Michael P F MPF Teng Zhongzhao Z

Annals of biomedical engineering 20170330 6

The rupture of an atherosclerotic plaque in the coronary circulation remains the main cause of heart attack. As a fiber-oriented structure, the fiber structure, in particular in the fibrous cap (FC), may affect both loading and material strength in the plaque. However, the role of fiber orientation and dispersion in plaque rupture is unclear. Local orientation and dispersion of fibers were calculated for the shoulder regions, mid FC, and regions with intimal thickening (IT) from histological ima ...[more]

PMID: 28361184

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Project description:BackgroundPlaque rupture and acute atherothrombosis, resulting from continued progression of atherosclerotic plaques (APs), are major contributors to acute clinical events such as stroke or myocardial infarction. This article aimed to explore the gene signatures and potential molecular mechanisms in the progression and instability of APs and to identify novel biomarkers and interventional targets for AP rupture.MethodsThe microarray data were downloaded from the Gene Expression Omnibus (GEO) database and grouped into discovery and validation cohorts. In the discovery cohort, Weighted Gene Co-Expression Network Analysis was performed for finding co-expression modules, and the Metascape database was used to perform functional enrichment analysis. Differential Expression Genes analysis subsequently was performed in the validation cohort for verification of the obtained results. Common genes were introduced into Metascape database for protein-protein interaction and functional enrichment analysis. We constructed the miRNAs-mRNAs network with the hub genes. Moreover, gene expression profiles of peripheral blood mononuclear cells (PBMCs) from peripheral blood of patients with plaque rupture were analyzed by high-throughput sequencing, and the diagnostic power of hub genes was verified by receiver operating characteristic (ROC) analysis.ResultsIn the discovery cohort, the brown module in GSE28829 and the turquoise module in GSE163154 were the most significant co-expression modules. Functional enrichment analysis of shared genes suggested that "Neutrophil degranulation" was the most significantly enriched pathway. These conclusions were also demonstrated by the validation cohort. A total of 16 hub genes were identified. The miRNA-mRNA network revealed that hsa-miR-665 and hsa-miR-512-3p might regulate the "Neutrophil degranulation" pathway through PLAU and SIRPA, which might play a significant role in AP progression and instability. Five hub genes, including PLAUR, FCER1G, PLAU, ITGB2, and SLC2A5, showed significantly increased expression in PBMCs from patients with plaque rupture compared with controls. ROC analysis finally identified three hub genes PLAUR, FCER1G, and PLAU that could effectively distinguish patients with APs rupture from controls.ConclusionsThe present study demonstrated that the "neutrophil degranulation" signaling pathways and identified novel mRNA and miRNA candidates are closely associated with plaque progression and instability. The hub genes FCER1G, PLAUR, and PLAU may serve as biomarkers for the prospective prediction of AP rupture.

Dataset Information

Impact of Fiber Structure on the Material Stability and Rupture Mechanisms of Coronary Atherosclerotic Plaques.

Publications

Impact of Fiber Structure on the Material Stability and Rupture Mechanisms of Coronary Atherosclerotic Plaques.

Similar Datasets

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