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Fibrinopeptide A induces C‐reactive protein expression through the ROS‐ERK1/2/p38‐NF‐κB signal pathway in the human umbilical vascular endothelial cells
Author(s) -
Zhao Jing,
Xu Shouzhu,
Liu Juntian
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28027
Subject(s) - p38 mitogen activated protein kinases , nadph oxidase , proinflammatory cytokine , chemistry , umbilical vein , signal transduction , reactive oxygen species , inflammation , endothelial dysfunction , nf κb , endothelial activation , oxidative stress , tumor necrosis factor alpha , superoxide , microbiology and biotechnology , immunology , biology , biochemistry , endocrinology , mapk/erk pathway , enzyme , in vitro
Atherosclerosis is a chronic inflammatory disease of the arterial wall. Inflammation causes endothelial injury and dysfunction, which is an initial step of atherosclerosis. Fibrinopeptide A (FPA) is a biomarker of the activation of the coagulation system, and a high concentration of FPA in the blood occurs in patients with ischemic cardiocerebrovascular diseases. The present research observed that FPA stimulated the generation of C‐reactive protein (CRP), IL‐1 β , and IL‐6 in human umbilical vascular endothelial cells (HUVECs); and anti‐IL‐1 β and anti‐IL‐6 neutralizing antibodies did not alter FPA‐induced CRP expression in HUVECs. The subchronic administration of FPA into rats increased the plasma FPA and CRP levels. Further studies showed that FPA stimulated superoxide anion generation, activated ERK1/2 and p38, promoted nuclear factor κB (NF‐κB) nuclear translocation, and raised the NF‐κB level in the nuclei of HUVECs. Antioxidant N‐acetylcysteine (NAC), complex II inhibitor thenoyltrifluoroacetone (TTFA), and NADPH oxidase inhibitor diphenyleneiodonium (DPI) inhibited FPA‐stimulated generation of superoxide anion, and NAC reduced FPA‐induced expressions of the phosphorylated ERK1/2 and p38. NAC, TTFA, DPI, inhibitors of ERK1/2, p38, and NF‐κB all downregulated FPA‐induced CRP expression. These results indicate that FPA induces CRP expression in HUVECs via the ROS‐ERK1/2/p38‐NF‐κB signal pathway. Moreover, this is the first report that FPA produces a proinflammatory effect on the vascular endothelial cells.