Gene Expression Profiling of Pulmonary Artery in a Rabbit Model of Pulmonary Thromboembolism

Abstract

Acute pulmonary thromboembolism (PTE) refers to the obstruction of thrombus in pulmonary artery or its branches. Recent studies have suggested that PTE-induced endothelium injury is the major physiological consequence of PTE. And it is reasonal to use PTE-induced endothelium injury to stratify disease severity. According to the massive morphologic and histologic findings, rabbit models could be applied to closely mimic the human PE. Genomewide gene expression profiling has not been attempted in PTE. In this study, we determined the accuracy of rabbit autologous thrombus PTE model for human PTE disease, then we applied gene expression array to identify gene expression changes in pulmonary arteries under PTE to identify potential molecular biomarkers and signaling pathways for PTE. We detected 1343 genes were upregulated and 923 genes were downregulated in PTE rabbits. The expression of several genes (IL-8, TNF-α, and CXCL5) with functional importance were further confirmed in transcript and protein levels. The most significantly differentially regulated genes were related to inflammation, immune disease, pulmonary disease, and cardiovascular diseases. Totally 87 genes were up-regulated in the inflammatory genes. We conclude that gene expression profiling in rabbit PTE model could extend the understanding of PTE pathogenesis at the molecular level. Our study provides the fundamental framework for future clinical research on human PTE, including identification of potential biomarkers for prognosis or therapeutic targets for PTE.

Bioinformatics-based study to detect chemical compounds that show potential as treatments for pulmonary thromboembolism

“…The RNA expression profiling dataset of the European rabbit ( Oryctolagus cuniculus ) was obtained from the GEO database in the National Center for Biotechnology Information ( http://www.ncbi.nlm.nih.gov/geo/ ; accession no. GSE84738) ( 13 ). The dataset included eight samples (four control samples and four PTE samples), collected from rabbit pulmonary artery tissue.…”

“…Furthermore, it is reported that troponin I, D-dimer, and plasma tenascin-C are positively correlated with the occurrence of PTE, whereas the erythrocyte sedimentation rate is downregulated in patients with PTE ( 12 ). Tang et al identified interleukin 8 ( IL‑8 ), tumor necrosis factor-α ( TNF‑α ), and C‑X‑C motif chemokine ligand 5 as important factors in PTE in rabbits ( 13 ). In addition, it was revealed that these important genes are associated with cardiovascular disease, pulmonary disease, immune disease, and inflammation ( 13 ).…”

“…Tang et al identified interleukin 8 ( IL‑8 ), tumor necrosis factor-α ( TNF‑α ), and C‑X‑C motif chemokine ligand 5 as important factors in PTE in rabbits ( 13 ). In addition, it was revealed that these important genes are associated with cardiovascular disease, pulmonary disease, immune disease, and inflammation ( 13 ). However, small chemical molecules targeting differently expressed genes (DEGs) between the PTE group and the control group did not screen out.…”

Successful reduction of inflammatory responses and arachidonic acid–cyclooxygenase 2 pathway in human pulmonary artery endothelial cells by silencing adipocyte fatty acid-binding protein

“…Our previous studies showed that the expression of FABP4 is increased in an animal model of PTE [ 7 ]. FABP4 is a key enzyme in the regulation of intracellular lipid metabolism and, in turn, lipid metabolism is linked to inflammatory response [ 8 ].…”

Mechanical Regulation of Protein Translation in the Cardiovascular System

“…Mechanical forces are also implicated in lung diseases, for example, force imbalances arising from pulmonary hypertension can remodel the pulmonary vasculature and induce smooth muscle and fibroblast proliferation in conjunction with increased collagen and elastin protein synthesis and gene expression (Wirtz and Dobbs, 2000). Disturbed mechanical forces exerted on pulmonary vascular endothelial cells induces changes in protein synthesis and expression of pro-inflammatory molecules such as IL-8, TNF-α and CXCL5 (Tang et al, 2016).…”