Aspirin modulates the inflammatory response in a thrombus‑stimulated LMVEC model

Abstract

The purpose of the present study was to examine whether aspirin interferes with the inflammatory response in a thrombus-stimulated lung microvascular endothelial cell (LMVEC) model. The LMVECs were randomly divided into eight groups: Normal group (group N), model group (group M), model + ASP group (group M+A), model+CX3CL1-short hairpin (sh)RNA group (group M+SH), model + CX3CL1-overexpression vector group (group M+CX3), model + ASP + shRNA group (group M+A+SH), model + ASP + CX3CL1-overexpression vector group (group M+A+CX3), and normal + virus control group (group N+V). The endothelial cells were cultured, and a thrombus was added to the cells. Briefly, 12 h following the precipitation of the thrombus, data from ELISA, reverse transcription-quantitative polymerase chain reaction analysis and confocal microscopy revealed that the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, CX3C chemokine ligand 1 (CX3CL1), CX3C chemokine receptor 1 (CX3CR1) and nuclear factor-κB (NF-κB) in group M were increased, compared with those in group N (P<0.01). These levels, with the exception of TNF-α, were significantly lower in group M+SH, compared with those in group M (P<0.01). Furthermore, the levels of IL-6 in groups M+A, M+CX3 and M+A+CX3 were decreased, compared with those in group M (P<0.01); the level of TNF-α in group M+A+SH was decreased, compared with that in group M (P<0.01); the level of CX3CR1 waslower in groups M+A and M+A+SH, compared with that in group M (P<0.01), and the level of NF-κB in group M+SH was decreased, compared with the level in group M and group M+A (P<0.05). In conclusion, the thrombus-stimulated LMVEC model exhibited induced production of TNF-α, IL-6, CX3CL, CX3CR1, NF-κB and intercellular adhesion molecule-1. Furthermore, it was confirmed that the signaling pathways involving CX3CL1-NF-κB, IL-6 and TNF-α were partly inhibited by aspirin.

Atorvastan, Apsirin and Hydorxyurea for an Effective and Low-Cost Treatment in High-Risk Polycythemia Vera

“…It has pleiotropic effects in erythroid proliferation and differentiation, as well as in the prevention of thrombotic events, and sensitises cells to HU's mechanism of action, thus allowing for lower doses to be used. [12][13][14][15][16] As part of the treatment protocol for PV, ASA works as an antiplatelet agent to prevent thrombosis, and also acts as an inhibitor of the nuclear factor NF-κ-B p105 (NFKB1) protein, [17][18][19][20] an activator of hypoxia inducible factor (HIF)-1α. 21 Down regulation of NFKB1 by ASA may decrease erythropoiesis by decreasing HIF-1α activity.…”