Abstract
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. Conclusion-: 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.
Original language | English (US) |
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Pages (from-to) | 643-649 |
Number of pages | 7 |
Journal | Arteriosclerosis, thrombosis, and vascular biology |
Volume | 31 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2011 |
Keywords
- NO
- NO synthase
- NOSTRIN
- PECAM-1
- endothelial function
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine