Platelet-Endothelial Cell Adhesion Molecule-1 Regulates Endothelial NO Synthase Activity and Localization Through Signal Transducers and Activators of Transcription 3-Dependent NOSTRIN Expression

被引:32
作者
McCormick, Margaret E. [1 ]
Goel, Reema [3 ]
Fulton, David [4 ]
Oess, Stefanie [5 ]
Newman, Debra [3 ]
Tzima, Ellie [1 ,2 ]
机构
[1] Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, McAllister Heart Inst, Chapel Hill, NC 27599 USA
[3] BloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI USA
[4] Med Coll Georgia, Vasc Biol Ctr, Augusta, GA 30912 USA
[5] Goethe Univ Frankfurt, Sch Med, Inst Biochem 2, Frankfurt, Germany
基金
美国国家卫生研究院;
关键词
endothelial function; NO; NO synthase; NOSTRIN; PECAM-1; NITRIC-OXIDE SYNTHASE; SHEAR-STRESS; MICE LACKING; PROTEIN; PECAM-1; GOLGI; FLOW; ENOS; CAVEOLIN-1; ATHEROSCLEROSIS;
D O I
10.1161/ATVBAHA.110.216200
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (Arterioscler Thromb Vasc Biol. 2011;31:643-649.)
引用
收藏
页码:643 / 649
页数:7
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