Transgenic expression of human C-reactive protein suppresses endothelial nitric oxide synthase expression and bioactivity after vascular injury.
C-reactive protein (CRP) is a risk marker and a potential modulator of vascular disease. Whether CRP modulates nitric oxide (NO) synthase (NOS) activity and NO metabolism remains unclear. We studied the effect of CRP on NO metabolism in transgenic mice that express human CRP (CRPtg). CRPtg and wild-type mice were subjected to controlled femoral artery wire injury. CRP serum levels at baseline and 6 and 24 h after injury were 12.4 +/- 9, 18.6 +/- 6.9, and 58.4 +/- 13 mg/l, respectively, in CRPtg mice but were undetectable at all time points in wild-type mice. Endothelial NOS protein and mRNA expression were significantly suppressed in the injured arteries of CRPtg mice (n = 5, P < 0.05). A similar reduction in eNOS expression was observed in the distant lung and heart. NO release after injury was significantly lower in CRPtg mice, as measured by nitrate and nitrite breakdown products, with a concomitant suppression of cGMP NO signaling after injury. Endothelial NOS and NO expression after vascular injury are locally and systemically suppressed in mice that express human CRP. These in vivo observations support the hypothesis that CRP modulates NO metabolism and may have implications regarding the mechanisms by which CRP modulates vascular disease.
Grad
Etty
E
Cardiovascular Research Center, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Golomb
Mordechai
M
Mor-Yosef
Irit
I
Koroukhov
Nikolay
N
Lotan
Chaim
C
Edelman
Elazer R
ER
Danenberg
Haim D
HD
D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000276:immunology*; D005263:Femoral Artery / Q000276:immunology* / Q000293:injuries*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D052250:Nitric Oxide Synthase Type III / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D019076:Transgenes
D002097:C-Reactive Protein; D052250:Nitric Oxide Synthase Type III