| First Author | McCormick ME | Year | 2011 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 31 |
| Issue | 3 | Pages | 643-9 |
| PubMed ID | 21183735 | Mgi Jnum | J:184177 |
| Mgi Id | MGI:5320389 | Doi | 10.1161/ATVBAHA.110.216200 |
| Citation | McCormick ME, et al. (2011) Platelet-endothelial cell adhesion molecule-1 regulates endothelial NO synthase activity and localization through signal transducers and activators of transcription 3-dependent NOSTRIN expression. Arterioscler Thromb Vasc Biol 31(3):643-9 |
| abstractText | BACKGROUND: NO produced by the endothelial NO synthase (eNOS) is an important regulator of cardiovascular physiological and pathological features. eNOS is activated by numerous stimuli, and its activity is tightly regulated. Platelet-endothelial cell adhesion molecule-1 (PECAM-1) has been implicated in regulating eNOS activity in response to shear stress. The current study was conducted to determine the role of PECAM-1 in the regulation of basal eNOS activity. METHODS AND RESULTS: We demonstrate that PECAM-1-knockout ECs have increased basal eNOS activity and NO production. Mechanistically, increased eNOS activity is associated with a decrease in the inhibitory interaction of eNOS with caveolin-1, impaired subcellular localization of eNOS, and decreased eNOS traffic inducer (NOSTRIN) expression in the absence of PECAM-1. Furthermore, we demonstrate that activation of blunted signal transducers and activators of transcription 3 (STAT3) in the absence of PECAM-1 results in decreased NOSTRIN expression via direct binding of the signal transducers and activators of transcription 3 to the NOSTRIN promoter. CONCLUSIONS: Our results reveal an elegant mechanism of eNOS regulation by PECAM-1 through signal transducers and activators of transcription 3-mediated transcriptional control of NOSTRIN. |
