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Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress.

ABSTRACT: Epigenomic changes in the venous cells exerted by oscillatory shear stress towards the endothelium may result in consolidation of gene expression alterations upon vein wall remodeling during varicose transformation. We aimed to reveal such epigenome-wide methylation changes. Primary culture cells were obtained from non-varicose vein segments left after surgery of 3 patients by growing the cells in selective media after magnetic immunosorting. Endothelial cells were either exposed to oscillatory shear stress or left at the static condition. Then, other cell types were treated with preconditioned media from the adjacent layer's cells. DNA isolated from the harvested cells was subjected to epigenome-wide study using Illumina microarrays followed by data analysis with GenomeStudio (Illumina), Excel (Microsoft), and Genome Enhancer (geneXplain) software packages. Differential (hypo-/hyper-) methylation was revealed for each cell layer's DNA. The most targetable master regulators controlling the activity of certain transcription factors regulating the genes near the differentially methylated sites appeared to be the following: (1) HGS, PDGFB, and AR for endothelial cells; (2) HGS, CDH2, SPRY2, SMAD2, ZFYVE9, and P2RY1 for smooth muscle cells; and (3) WWOX, F8, IGF2R, NFKB1, RELA, SOCS1, and FXN for fibroblasts. Some of the identified master regulators may serve as promising druggable targets for treating varicose veins in the future.

SUBMITTER: Smetanina MA

PROVIDER: S-EPMC10048778 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress.

Smetanina Mariya A MA Korolenya Valeria A VA Kel Alexander E AE Sevostyanova Ksenia S KS Gavrilov Konstantin A KA Shevela Andrey I AI Filipenko Maxim L ML

Epigenomes 20230320 1

Epigenomic changes in the venous cells exerted by oscillatory shear stress towards the endothelium may result in consolidation of gene expression alterations upon vein wall remodeling during varicose transformation. We aimed to reveal such epigenome-wide methylation changes. Primary culture cells were obtained from non-varicose vein segments left after surgery of 3 patients by growing the cells in selective media after magnetic immunosorting. Endothelial cells were either exposed to oscillatory ...[more]

PMID: 36975604

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Project description:IntroductionWall shear stress (WSS) and oscillatory shear index (OSI) are associated with atherosclerotic disease. Both parameters are derived from blood velocities, which can be measured with phase-contrast MRI (PC-MRI). Limitations in spatiotemporal resolution of PC-MRI are known to affect these measurements. Our aim was to investigate the effect of spatiotemporal resolution using a carotid artery phantom.MethodsA carotid artery phantom was connected to a flow set-up supplying pulsatile flow. MRI measurement planes were placed at the common carotid artery (CCA) and internal carotid artery (ICA). Two-dimensional PC-MRI measurements were performed with thirty different spatiotemporal resolution settings. The MRI flow measurement was validated with ultrasound probe measurements. Mean flow, peak flow, flow waveform, WSS and OSI were compared for these spatiotemporal resolutions using regression analysis. The slopes of the regression lines were reported in %/mm and %/100ms. The distribution of low and high WSS and OSI was compared between different spatiotemporal resolutions.ResultsThe mean PC-MRI CCA flow (2.5±0.2mL/s) agreed with the ultrasound probe measurements (2.7±0.02mL/s). Mean flow (mL/s) depended only on spatial resolution (CCA:-13%/mm, ICA:-49%/mm). Peak flow (mL/s) depended on both spatial (CCA:-13%/mm, ICA:-17%/mm) and temporal resolution (CCA:-19%/100ms, ICA:-24%/100ms). Mean WSS (Pa) was in inverse relationship only with spatial resolution (CCA:-19%/mm, ICA:-33%/mm). OSI was dependent on spatial resolution for CCA (-26%/mm) and temporal resolution for ICA (-16%/100ms). The regions of low and high WSS and OSI matched for most of the spatiotemporal resolutions (CCA:30/30, ICA:28/30 cases for WSS; CCA:23/30, ICA:29/30 cases for OSI).ConclusionWe show that both mean flow and mean WSS are independent of temporal resolution. Peak flow and OSI are dependent on both spatial and temporal resolution. However, the magnitude of mean and peak flow, WSS and OSI, and the spatial distribution of OSI and WSS did not exhibit a strong dependency on spatiotemporal resolution.

Project description:IntroductionSpontaneous vertebral artery dissection (sVAD) might tend to develop in vertebral artery hypoplasia (VAH) with hemodynamic dysfunction and it is crucial to assess hemodynamics in sVAD with VAH to investigate this hypothesis. This retrospective study aimed to quantify hemodynamic parameters in patients with sVAD with VAH.MethodsPatients who had suffered ischemic stroke due to an sVAD of VAH were enrolled in this retrospective study. The geometries of 14 patients (28 vessels) were reconstructed using Mimics and Geomagic Studio software from CT angiography (CTA). ANSYS ICEM and ANSYS FLUENT were utilized for mesh generation, set boundary conditions, solve governing equations, and perform numerical simulations. Slices were obtained at the upstream area, dissection or midstream area and downstream area of each VA. The blood flow patterns were visualized through instantaneous streamline and pressure at peak systole and late diastole. The hemodynamic parameters included pressure, velocity, time-averaged blood flow, time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), endothelial cell action potential (ECAP), relative residence time (RRT) and time-averaged nitric oxide production rate (TARNO).ResultsSignificant focal increased velocity was present in the dissection area of steno-occlusive sVAD with VAH compared to other nondissected areas (0.910 m/s vs. 0.449 vs. 0.566, p < 0.001), while focal slow flow velocity was observed in the dissection area of aneurysmal dilatative sVAD with VAH according to velocity streamlines. Steno-occlusive sVAD with VAH arteries had a lower time-averaged blood flow (0.499 cm3/s vs. 2.268, p < 0.001), lower TAWSS (1.115 Pa vs. 2.437, p = 0.001), higher OSI (0.248 vs. 0.173, p = 0.006), higher ECAP (0.328 Pa-1 vs. 0.094, p = 0.002), higher RRT (3.519 Pa-1 vs. 1.044, p = 0.001) and deceased TARNO (104.014 nM/s vs. 158.195, p < 0.001) than the contralateral VAs.ConclusionSteno-occlusive sVAD with VAH patients had abnormal blood flow patterns of focal increased velocity, low time-averaged blood flow, low TAWSS, high OSI, high ECAP, high RRT and decreased TARNO. These results provide a good basis for further investigation of sVAD hemodynamics and support the applicability of the CFD method in testing the hemodynamic hypothesis of sVAD. More detailed hemodynamic conditions with different stages of sVAD are warranted in the future.

Dataset Information

Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress.

Publications

Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress.

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