Porcine Aortic Endothelial Cell Genes Responsive to Selected Inflammatory Stimulators

Abstract

ABSTRACT. Use of porcine tissues has been suggested as a promising solution for severe shortage of transplantable human organs. The immediate hurdle for xenotransplantation is acute immune/inflammatory vascular rejection of the transplant. Because endothelial cells play a key role in the initiation and the amplification of inflammation, alteration of gene expression in human endothelial cells, by various inflammatory stimulators has been studied extensively. However, transcriptional changes induced by human and other inflammatory stimulators in porcine endothelial cells have thus far not been studied. In this study, we treated porcine endothelial cells with human tumor necrosis factor (TNF)-, porcine interferon (IFN)-, H 2 O 2 and lypopolysaccharide (LPS) and profiled transcriptional change at 1 hr, 6 hr and 24 hr, using pig oligonucleotide 13K microarray. We found that mRNA species such as chemokine (C-X-C motif) ligand 6 (CXCL6) and Cathepsin S were significantly induced in porcine endothelial cells, as was previously reported with human endothelial cell. We also found that mRNA species including secreted frizzled-related protein 2 (SFRP2), radical S-adenosyl methionine domain containing 2 (RSAD2), structure specific recognition protein 1 (SSRP1) also were highly overexpressed in porcine endothelial cells. This result shows clues to understand underlying mechanisms of xenotransplantation rejection and the highly responsive porcine genes may serve as novel targets to be regulated for improving the function of grafted porcine donor organs.

Effect of TNF‐alpha blockade on coagulopathy and endothelial cell activation in xenoperfused porcine kidneys

“…Application of TNF‐RFP leads to prolonged perfusion time, lower RVR, and a reduction in the endothelial cell activation, as shown by the suppression of the adhesion molecules ICAM‐1, VCAM‐1, and E‐selectin. The expression of these adhesion molecules is induced in response to inflammatory stimuli such as TNF‐alpha after binding to its receptor via the transcription of NFKB . The prolonged perfusion time and the lower RVR can be explained by the reduction in vasoconstriction and inflammation.…”

“…Immediately after reperfusion, the graft's endothelium is activated promoting a procoagulatory and proinflammatory matrix, contributing to the rejection process of HAR and AHXR . Binding of antibodies to gal and non‐gal epitopes on porcine endothelium and inflammatory stimuli such as TNF‐alpha can activate porcine endothelial cells as well as ischemic reperfusion injury. Activated endothelium itself can interact with the recipients’ leukocytes and thrombocytes, which in turn activates these cells .…”

Changes in Gene Expression of Pial Vessels of the Blood Brain Barrier during Murine Neurocysticercosis

“…Network analysis shows that apart from transporters several other sets of immune related genes including MRC1, complements (C3, C6, and C1R and complement factor properdin), TNF super family members and interferon inducible genes including STAT1 are induced in NCC infection which can potentially lead to endothelial cell activation [23], [24], [28]. Interferon inducible genes have been shown to be induced in an in vitro study with endothelial cells in HIV and Cryptococcus neoformans infection model [25], [29].…”

“…STAT1 has been shown to promote inflammatory mediators and leukocyte transmigration at the BBB [30]. Interferon signaling mediated through the Jak Stat pathway is critical to induce several of these genes in endothelial cells including chemokines and MHC class I antigen presentation related genes [23], [24], [28].…”