| First Author | Lee SJ | Year | 2013 |
| Journal | Cardiovasc Res | Volume | 99 |
| Issue | 4 | Pages | 724-33 |
| PubMed ID | 23720274 | Mgi Jnum | J:219262 |
| Mgi Id | MGI:5619939 | Doi | 10.1093/cvr/cvt135 |
| Citation | Lee SJ, et al. (2013) 5-Lipoxygenase plays a pivotal role in endothelial adhesion of monocytes via an increased expression of Mac-1. Cardiovasc Res 99(4):724-33 |
| abstractText | AIMS: 5-Lipoxygenase (5-LO) is known to participate in the pathogenesis of atherosclerosis; however, the underlying mechanisms are unclear. Thus, this study investigated the molecular mechanisms responsible for 5-LO expression in monocytes as well as the role of 5-LO in monocyte adhesion to the vascular endothelium, which is a key early event in macrophage foam cell formation. METHODS AND RESULTS: An en face immunohistochemistry of endothelial surfaces revealed a marked increase in monocyte adhesion to the aortic endothelium in wild-type (WT) mice treated with lipopolysaccharide (LPS), which was significantly attenuated in 5-LO((-/-)) mice. Likewise, the adhesion capacity of primary monocytes isolated from LPS-treated WT mice was higher than those of monocytes from 5-LO((-/-)) mice. In in vitro study, LPS increased monocyte adhesion to endothelial cells with an enhanced Mac-1 expression. These were attenuated by a 5-LO inhibitor, MK886, as well as by molecular depletion of 5-LO in monocytes. Furthermore, LPS-induced Mac-1 expression on monocytes was significantly inhibited by pre-treatment with U-75302, a BLT1-receptor antagonist, suggesting a pivotal role of 5-LO-derived leukotrienes. In promoter activity analysis and chromatin immunoprecipitation assays to identify transcription factors involved in 5-LO expression, both NF-kappaB and Sp1 played central roles to increase 5-LO expression in LPS-treated monocytes. CONCLUSION: 5-LO expression in monocytes is modulated via NF-kappaB and Sp1 signalling pathways, and 5-LO plays a pivotal role in LPS-mediated monocyte adhesion to the vascular endothelium through an increased expression of Mac-1 on monocytes. |
