Transcriptomic Profiling of Femoral Veins in Deep Vein Thrombosis in a Porcine Model

Abstract

Deep vein thrombosis (DVT) is a severe disease affecting the human venous system, accompanied by high morbidity and mortality rates caused by early and late complications. The study aimed at analyzing the changes in the transcriptome of the femoral vein caused by DVT in the porcine model based on the formation of the thrombus in vivo. The study was performed on 11 castrated male pigs: a thrombus was formed in each left femoral vein in six animals; the remaining five served as a control group. Total RNA was isolated from the left femoral veins of the experimental and control animals. High-throughput RNA sequencing was used to analyze the global changes in the transcriptome of veins with induced DVT. Applied multistep bioinformatics revealed 1474 differentially expressed genes (DEGs): 1019 upregulated and 455 downregulated. Functional Gene Ontology annotated 1220 of DEGs into 225 biological processes, 30 molecular functions and 40 cellular components categories. KEGG analysis disclosed TNF, NF-κB and apoptosis pathways’ overexpression in DVT samples. A thorough analysis of the detected DEGs indicated that a dysregulated inflammatory response and disturbed balance between clotting and anti-clotting factors play a crucial role in the process of DVT.

A vein wall cell atlas of murine venous thrombosis determined by single-cell RNA sequencing

“…The precise roles of each vascular and immune cell population in thrombus formation, resolution, and post-thrombotic vein wall remodeling are incompletely understood. Studies using bulk RNA sequencing to examine early transcriptomic changes in the vein wall across murine 12 and porcine 13 models of DVT have been performed. However, the molecular signature of DVT within the vein wall at single-cell resolution is still unknown.…”

Pulmonary artery embolism: comprehensive transcriptomic analysis in understanding the pathogenic mechanisms of the disease

“…The current research, which aimed at analyzing the changes in the transcriptome of PA with induced PE, is the continuation of our previous studies devoted to the transcriptomic profiling of femoral veins in DVT. We mainly disclosed that dysregulation of TNF, NF-κB, and apoptosis pathways affect inflammatory responses and the formation, remodeling, and resolution of thrombus in the course of DVT [ 16 ]. Whilst, the present project not only uncovered the genetic biomarkers of PE but also unrevealed that the disturbed homeostasis in the biosynthesis of proteins in the ER plays a major role in the pathogenesis of PE.…”

“…A previous analysis of the changes in the transcriptome of the femoral vein caused by DVT in the porcine model based on the formation of the thrombus in vivo, disclosed that TNF, NF-κB and apoptosis pathways are strongly dysregulated during the thrombus formation [ 16 ]. The present study also revealed genes with significant allelic imbalance involved in the TNFα signaling pathway, such as the Coiled-coil domain containing 3 (CCDC3), Thy-1 Cell Surface Antigen (Thy1) and TRAF2.…”

“…Further studies investigating the molecular background of thrombus formation and its effect on the venous and arterial endothelium in course of the DVT and PE are needed. Therefore, in our previous study, we already investigated the transcriptomic profile of femoral veins in DVT, and we discovered that dysregulation of TNF, NF-κB, and apoptosis pathways affect inflammatory responses and the formation, remodeling, and resolution of thrombus in DVT pathogenesis [ 16 ]. Whereas, the present research was aimed at analyzing the changes in the gene expression associated with PE in the PA samples (PA-E).…”

Incidence and Related Factors for Low-Extremity Deep Vein Thrombosis in Breast Cancer Patients Who Underwent Surgical Resection: What Do We Know and What Should We Care

“…Unfortunately, patients with breast cancer after resection may experience severe postoperative complications (8)(9)(10)(11). One of the most threatening complications is deep vein thrombosis (DVT), a severe disease in the venous system, which is a vital cause of high mortality of breast cancer (10,12,13).…”