Fibrinogen, fibrin, and FDP induce C-reactive protein generation in rat vascular smooth muscle cells: pro-inflammatory effect on atherosclerosis.
Atherosclerosis is a chronic inflammatory disease in the vessel. As an inflammatory cytokine, C-reactive protein (CRP) participates in the pathogenesis of atherosclerosis through multiple bioactivities. It has been widely accepted that hyperfibrinogenemia is associated with the formation and progression of atherosclerosis. But, it is unknown whether fibrinogen exerts a pro-inflammatory effect on vascular smooth muscle cells (VSMCs). The purpose of the present study was to observe the effect of fibrinogen, fibrin, and fibrin degradation products (FDP) on CRP generation in VSMCs. CRP mRNA expression was identified with the reverse transcription polymerase chain reaction. CRP level in the supernatant of VSMCs was measured with the enzyme-linked immunosorbent assay. CRP expression in VSMCs was examined with the immunocytochemical method. The results showed that fibrinogen, fibrin, and FDP all induced CRP production in VSMCs both in mRNA level and in protein level in a time- and concentration-dependent manner. The potency is FDP>fibrin>fibrinogen, which seems to mean that their pro-inflammatory activity decreases with increase of molecular weight of these three proteins. The finding provides a new mechanism for atherogenic effect of fibrin(ogen) and FDP, and emphasizes the importance of therapy of hyperfibrinogenemia in atherosclerosis.
Department of Pharmacology, Xi'an Jiaotong University School of Medicine, People's Republic of China.
Fang
F
Guo
Juntian
J
Liu
Chenjing
C
Wang
Na
N
Liu
Peipei
P
Lu
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D002097:C-Reactive Protein / Q000096:biosynthesis*; D002478:Cells, Cultured; D005337:Fibrin / Q000378:metabolism* / Q000494:pharmacology; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism* / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D005338:Fibrin Fibrinogen Degradation Products; D005337:Fibrin; D005340:Fibrinogen; D002097:C-Reactive Protein