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Series GSE263281 Query DataSets for GSE263281
Status Public on May 29, 2024
Title Spatial gene expression of canine veins during carotid-cartoid vein bypass implantation
Organism Canis lupus familiaris
Experiment type Other
Summary Vein graft failure (VGF) following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. Vein graft injury can occur during autogenous vein harvest and preparation, as well as after implantation into the arterial system, leading to the development of intimal hyperplasia, vein graft stenosis, and, ultimately, bypass graft failure. While previous studies have identified maladaptive pathways that occur shortly after implantation, the specific signaling pathways that occur during vein graft preparation are not well defined and may result in a cumulative impact on VGF. We, therefore, aimed to elucidate the response of the vein conduit wall during harvest and following implantation, probing the key maladaptive pathways driving graft failure with the overarching goal of identifying therapeutic targets for biologic intervention to minimize these natural responses to surgical vein graft injury. Employing a novel approach to investigating vascular pathologies, we harnessed both single-nuclei RNA-sequencing (snRNA-seq) and spatial transcriptomics (ST) analyses to profile the genomic effects of vein grafts after harvest and distension, then compared these findings to vein grafts obtained 24 hours after carotid-cartoid vein bypass implantation in a canine model (n=4). Collectively, we find that vein conduit harvest and distension elicit a prompt genomic response facilitated by distinct cellular subpopulations heterogeneously distributed throughout the vein wall. This response was found to be further exacerbated following vein graft implantation, resulting in a cascade of maladaptive gene regulatory networks. Together, these results suggest that distension initiates the upregulation of pathological pathways that may ultimately contribute to bypass graft failure and presents potential early targets warranting investigation for targeted therapies.
Overall design Bilateral upper limb cephalic vein harvest and carotid-cartoid vein bypass implantation were performed on 25 kg male (n=3) or female (n=1) mongrel dogs. Samples (15 cm) of distended vein were taken following distension during graft harvesting and at 24 hours post-bypass, alongside untouched control vein samples, and embedded in OCT blocks and flash-frozen in an isopentane and liquid nitrogen bath for spatial transcriptomics analysis.
Web link
Contributor(s) Marina M, Lucas M, Patric L, Manoj B
Citation(s) 38808504
Submission date Apr 05, 2024
Last update date May 30, 2024
Contact name Marina Michaud
Phone 4043078082
Organization name Emory University
Department School of Medicine
Lab Bhasin Lab
Street address 28 Cass Station Dr NW
City Cartersville
State/province GA
ZIP/Postal code 30120
Country USA
Platforms (1)
GPL25760 Illumina NovaSeq 6000 (Canis lupus familiaris)
Samples (8)
GSM8189150 Control vein, canine 1, ST
GSM8189151 Grafted vein, canine 1, ST
GSM8189152 Control vein, canine 2, ST
BioProject PRJNA1096624

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GSE263281_RAW.tar 44.1 Mb (http)(custom) TAR (of MTX, TAR, TSV)
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Raw data are available in SRA

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