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) |
|---|---|
| Pages (from-to) | 643-649 |
| Number of pages | 7 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Volume | 31 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2011 |
Fingerprint
Keywords
- NO
- NO synthase
- NOSTRIN
- PECAM-1
- endothelial function
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Platelet-endothelial cell adhesion molecule-1 regulates endothelial NO synthase activity and localization through signal transducers and activators of transcription 3-dependent NOSTRIN expression. / McCormick, Margaret E.; Goel, Reema; Fulton, David; Oess, Stefanie; Newman, Debra; Tzima, Ellie.
In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 31, No. 3, 01.03.2011, p. 643-649.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Platelet-endothelial cell adhesion molecule-1 regulates endothelial NO synthase activity and localization through signal transducers and activators of transcription 3-dependent NOSTRIN expression
AU - McCormick, Margaret E.
AU - Goel, Reema
AU - Fulton, David
AU - Oess, Stefanie
AU - Newman, Debra
AU - Tzima, Ellie
PY - 2011/3/1
Y1 - 2011/3/1
N2 - 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.
AB - 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.
KW - NO
KW - NO synthase
KW - NOSTRIN
KW - PECAM-1
KW - endothelial function
UR - http://www.scopus.com/inward/record.url?scp=79952188007&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952188007&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.110.216200
DO - 10.1161/ATVBAHA.110.216200
M3 - Article
C2 - 21183735
AN - SCOPUS:79952188007
VL - 31
SP - 643
EP - 649
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 3
ER -