C-reactive protein directly inhibits nitric oxide production by cytokine-stimulated vascular smooth muscle cells.
C-reactive protein (CRP) is an important risk factor for atherosclerosis and coronary artery disease. The authors investigated the effects of CRP on nitric oxide (NO) synthesis in vascular smooth muscle cells (VSMCs). Production of nitrite, a stable metabolite of NO, was measured, as was the expression of inducible NO synthase (iNOS) messenger RNA and protein in cultured rat VSMCs. Incubation of cultures with interleukin (IL)-1beta (10 ng/mL) caused a significant increase in nitrite production. C-reactive protein significantly decreased the IL-1beta-induced nitrite production by VSMCs in a dose-dependent manner (10-100 microg/mL). Incubation with IL-1beta induced expression of iNOS mRNA and protein in VSMCs, whereas CRP showed a suppressive effect on their expression. Addition of IL-1beta activated nuclear factor-kappaB (NFkappaB) in VSMCs, whereas CRP did not affect IL-1beta-induced NFkappaB activation. In conclusion, CRP acts on VSMCs and inhibits NO synthesis, which might contribute to the development of atherosclerosis and vascular events.
Ikeda
Uichi
U
Department of Organ Regeneration, Shinshu University Graduate School of Medicine, Matsumoto, Japan. uikeda@sch.md.sinshu-u.ac.jp
Takahashi
Masafumi
M
Shimada
Kazuyuki
K
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002097:C-Reactive Protein / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D009569:Nitric Oxide; D002097:C-Reactive Protein; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat