| First Author | Ishikawa T | Year | 2013 |
| Journal | J Clin Invest | Volume | 123 |
| Issue | 8 | Pages | 3488-97 |
| PubMed ID | 23867501 | Mgi Jnum | J:201404 |
| Mgi Id | MGI:5514072 | Doi | 10.1172/JCI66533 |
| Citation | Ishikawa T, et al. (2013) LXRbeta/estrogen receptor-alpha signaling in lipid rafts preserves endothelial integrity. J Clin Invest 123(8):3488-97 |
| abstractText | Liver X receptors (LXR) are stimulated by cholesterol-derived oxysterols and serve as transcription factors to regulate gene expression in response to alterations in cholesterol. In the present study, we investigated the role of LXRs in vascular endothelial cells (ECs) and discovered that LXRbeta has nonnuclear function and stimulates EC migration by activating endothelial NOS (eNOS). This process is mediated by estrogen receptor-alpha (ERalpha). LXR activation promoted the direct binding of LXRbeta to the ligand-binding domain of ERalpha and initiated an extranuclear signaling cascade that requires ERalpha Ser118 phosphorylation by PI3K/AKT. Further studies revealed that LXRbeta and ERalpha are colocalized and functionally coupled in EC plasma membrane caveolae/lipid rafts. In isolated aortic rings, LXR activation of NOS caused relaxation, while in mice, LXR activation stimulated carotid artery reendothelialization via LXRbeta- and ERalpha-dependent processes. These studies demonstrate that LXRbeta has nonnuclear function in EC caveolae/lipid rafts that entails crosstalk with ERalpha, which promotes NO production and maintains endothelial monolayer integrity in vivo. |
