Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells.
BACKGROUND
C-reactive protein (CRP), the prototypic marker of inflammation, has been shown to be an independent predictor of cardiovascular events. Endothelial nitric oxide synthase (eNOS) deficiency is a pivotal event in atherogenesis.


RESULTS
We tested the effect of CRP on eNOS expression and bioactivity in cultured human aortic endothelial cells (HAECs). CRP decreased eNOS mRNA, protein abundance, and enzyme activity in HAECs. Furthermore, eNOS bioactivity assayed by cyclic GMP levels was significantly reduced by CRP. Preincubation of cells with CRP also significantly increased the adhesion of monocytes to HAECs.


CONCLUSIONS
CRP causes a direct reduction in eNOS expression and bioactivity in HAECs, further supporting its role in atherogenesis.
Venugopal
Senthil Kumar
SK
Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology, UC Davis Medical Center, Sacramento, Calif 95817, USA.
Devaraj
Sridevi
S
Yuhanna
Ivan
I
Shaul
Philip
P
Jialal
Ishwarlal
I
D001011:Aorta / Q000166:cytology / Q000201:enzymology*; D002097:C-Reactive Protein / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D009000:Monocytes / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic
D012333:RNA, Messenger; D002097:C-Reactive Protein; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III