Synergistic enhancement of matrix metalloproteinase-9 expression and pro-inflammatory cytokines by influenza virus infection and oxidized-LDL treatment in human endothelial cells

摘要

Oxidized low-density lipoprotein (oxLDL) has been reported to contribute to the development and progression of atherosclerosis, which is also stimulated by viral infections, such as influenza. However, the mechanism underlining the promotion of atherosclerosis by both risk factors remains unclear. In the present study, we investigated the expression of matrix metalloproteinase-9 (MMP-9), which is one of key mediators of atherosclerosis progression, in oxLDL-treated human umbilical vein endothelial cells (HUVEC)-C cells. The infection efficiency of H1N1 pdm2009 influenza virus in the HUVEC-C cells was subsequently examined, and the expression of MMP-9 and proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, were determined in the virus-infected HUVEC-C cells, with or without oxLDL treatment. Results demonstrated that oxLDL treatment with 10, 20 or 50 µg/ml markedly upregulated MMP-9 expression at the mRNA and protein levels. H1N1 pdm2009 influenza virus efficiently infected the HUVEC-C cells and significantly promoted the expression of MMP-9, TNF-α, IL-1β and IL-6, synergistically with the oxLDL treatment. Taken together, these results demonstrated for the first time that oxidized-LDL treatment and influenza virus infection synergistically enhance the expression of MMP-9 and proinflammatory cytokines in human endothelial cells, suggesting that both factors are potent stimulators in atherosclerotic impairment to endothelial cells.