| First Author | Zeng X | Year | 2018 |
| Journal | J Transl Med | Volume | 16 |
| Issue | 1 | Pages | 106 |
| PubMed ID | 29673358 | Mgi Jnum | J:319276 |
| Mgi Id | MGI:6863465 | Doi | 10.1186/s12967-018-1479-6 |
| Citation | Zeng X, et al. (2018) Contribution of TLR4 signaling in intermittent hypoxia-mediated atherosclerosis progression. J Transl Med 16(1):106 |
| abstractText | BACKGROUND: Intermittent hypoxia (IH), a typical character of obstructive sleep apnea (OSA), is related to atherogenesis. However, the role of IH on atherosclerosis (AS) progression and the mechanisms involved remains poorly understood. METHODS: In the present study, high-fat fed ApoE(-/-) mice were treated with recombinant shRNA-TLR4 lentivirus and exposed to IH. Atherosclerotic lesions on the en face aorta and cross-sections of aortic root were examined by Oil-Red O staining. The content of lipids and collagen of aortic root plaques were detected by Oil-Red O staining and Sirius red staining, respectively. The TLR4, NF-kappaB p65, alpha-SMA and MOMA-2 expression in aorta and IL-6 and TNF-alpha expression in the mice serum were also detected. RESULTS: Compared with the Sham group, the IH treated group further increased atherosclerotic plaque loads and plaque vulnerability in the aortic sinus. Along with increased TLR4 expression, enhanced NF-kappaB activation, inflammatory activity and aggravated dyslipidemia were observed in the IH treated group. TLR4 interference partly inhibited IH-mediated AS progression with decreased inflammation and improved cholesterol levels. Similarly, in endothelial cells, hypoxia/reoxygenation exposure has been shown to promote TLR4 expression and activation of proinflammatory TLR4/NF-kappaB signaling, while TLR4 interference inhibited these effects. CONCLUSIONS: We found that the IH accelerated growth and vulnerability of atherosclerotic plaque, which probably acted by triggering the activation of proinflammatory TLR4/NF-kappaB signaling. These findings may suggest that IH is a risk factor for vulnerable plaque and provide a new insight into the treatment of OSA-induced AS progression. |
