Identification of intima-to-media signals for flow-induced vascular remodeling using correlative gene expression analysis

Abstract

Changes in blood flow can induce arterial remodeling. Intimal cells sense flow and send signals to the media to initiate remodeling. However, the nature of such intima-media signaling is not fully understood. To identify potential signals, New Zealand white rabbits underwent bilateral carotid ligation to increase flow in the basilar artery or sham surgery (n = 2 ligated, n = 2 sham). Flow was measured by transcranial Doppler ultrasonography, vessel geometry was determined by 3D angiography, and hemodynamics were quantified by computational fluid dynamics. 24 h post-surgery, the basilar artery and terminus were embedded for sectioning. Intima and media were separately microdissected from the sections, and whole transcriptomes were obtained by RNA-seq. Correlation analysis of expression across all possible intima-media gene pairs revealed potential remodeling signals. Carotid ligation increased flow in the basilar artery and terminus and caused differential expression of 194 intimal genes and 529 medial genes. 29,777 intima-media gene pairs exhibited correlated expression. 18 intimal genes had > 200 medial correlates and coded for extracellular products. Gene ontology of the medial correlates showed enrichment of organonitrogen metabolism, leukocyte activation/immune response, and secretion/exocytosis processes. This demonstrates correlative expression analysis of intimal and medial genes can reveal novel signals that may regulate flow-induced arterial remodeling.

Vascular Cast to Program Antistenotic Hemodynamics and Remodeling of Vein Graft

“…The bridge addition most effectively supported the cast function to prevent intimal hyperplasia of veins, as evidenced by Verhoeff‐van Gieson staining of the vein cross‐sections with a quantitative analysis of the neointimal area, media thickness, and intima‐to‐media ratio in the test groups (Figure 4c ). [ 18 ] As a clear indication to preserve arterial flow (Figure 4d ), the bridge addition promoted the cast effects in inducing EC alignment significantly when compared to the other groups using en face staining of test veins. The flow directional alignment of ECs supported the maintenance of the tight junctions with increased aspect ratio and the reduced circularity, as observed in the quantitative analyses of cell morphology.…”

An Image-Based Workflow for Objective Vessel Wall Enhancement Quantification in Intracranial Aneurysms

“…To visualize and quantify VWE, we started by reconstructing 3D models from MRA data in order to provide the surface on which the intensities would be mapped. The MRA image was segmented and cleaned to generate a surface file using VMTK (www.vmtk.org, accessed 20 January 2020), as previously described [12]. To obtain all images into the same coordinate system, the non-enhanced and contrast-enhanced MR images were registered onto the raw MRA image using an open-source platform, 3D Slicer, which implemented the BRAINSFit module (https://www.slicer.org, accessed 20 January 2020) for mutualinformation rigid body transformation of the images.…”

Avaliação da incidência de Acidente Vascular Cerebral Isquêmico e sua relação com a espessura do Complexo Médio-intimal: Estudo Retrospectivo

“…O AVCi, forma mais comum de AVC, ocorre devido à obstrução de uma artéria por um trombo ou êmbolo, interrompendo a via de suplência da circulação cerebral e causando isquemia. As principais formas de oclusão desse subtipo da doença são as condições trombóticas, estreitamento dos vasos devido ao desenvolvimento de aterosclerose e as causas embólicas (Kolega, 2021;Porth & Matfin, 2010;Regattieri, 2012).…”