Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 47, Issue 1, Pages 266-278Publisher
KARGER
DOI: 10.1159/000489805
Keywords
Fibrinopeptide A; CRP; Vascular smooth muscle cells; Inflammation; Atherosclerosis
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Background/Aims: Atherosclerosis is a chronic inflammatory disease in the artery walls. Fibrinopeptide A (FPA) is a biomarker of the activation of coagulation system, and a high concentration of FPA in blood occurs in patients with ischemic heart disease etc. However, there exist few studies on the pathological effects of FPA in cardiovascular system. Therefore, the present study examined the effect of FPA on CRP expression in VSMCs and the molecular mechanisms. Methods: mRNA and protein expression was identified by quantitative real-time PCR and Western blot, respectively. Reactive oxygen species (ROS) and the immunofluorescence staining were observed by a fluorescence microscope. Plasma FPA and CRP level was determined by ELISA. Results: FPA induced the expressions of CRP, IL-1 beta and IL-6 in VSMCs, and anti-IL-1 beta and anti-IL-6 neutralizing antibodies partially reduced FPA-induced CRP expression in VSMCs. The subchronic administration of FPA to rats increased FPA level in plasma and CRP expression in the aortic artery walls. The further studies showed that FPA promoted superoxide anion generation in VSMCs. Antioxidant NAC antagonized FPA-stimulated superoxide anion generation and inhibited FPA-induced CRP expression in VSMCs. FPA activated ERK1/2 and p38 phosphorylation, and PD98059 and SB203580 reduced FPA-induced CRP expression. Moreover, NAC inhibited the activation of ERK1/2 and p38. In addition, FPA enhanced NF-kappa B level in the nuclei of VSMCs, and PDTC reduced FPA-induced expression of CRP. Conclusions: FPA induces CRP expression in VSMCs via ROS-ERK1/2/p38NF-kappa B signal pathway. This finding for the first time provides an experimental evidence for pro-inflammatory effect of FPA. (c) 2018 The Author(s) Published by S. Karger AG, Basel.
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