Fibrinopeptide A induces C‐reactive protein expression through the ROS‐ERK1/2/p38‐NF‐κB signal pathway in the human umbilical vascular endothelial cells

Abstract

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‐1β, 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.

Contra-Directional Expression of Plasma Superoxide Dismutase with Lipoprotein Cholesterol and High-Sensitivity C-reactive Protein as Important Markers of Parkinson’s Disease Severity

“…On the other hand, O 2 − has involved not just oxidative stress but also pro-inflammatory roles, which may contribute to the recruitment of neutrophils to sites of inflammation, the formation of chemotactic factors, cytokine release, neurotransmitter and hormone inactivation, adhesion molecules expression, lipid peroxidation and oxidation and DNA damage. Previous studies also indicated that O 2 − could activate nuclear factor-κB, which finally induced hsCRP expression (Zhao et al, 2019). SOD is the major antioxidant enzyme in the human antioxidant system to protect against oxidative stress, which catalyzes the dismutation of highly reactive O 2 − to less reactive H 2 O 2 and oxygen.…”

Septic serum mediates inflammatory injury in human umbilical vein endothelial cells via reactive oxygen species, mitogen activated protein kinases and nuclear factor‑κB

“…For the cell signaling pathway investigation, the cells were pre-treated with specific inhibitors for 1 h, followed by treatment with 10% septic serum. The concentrations of the specific inhibitors were as follows: 20 µM ERK 1/2 inhibitor PD98059; 10 µM p38 inhibitor SB203580; 20 µM JNK inhibitor SP600125; 10 µM antioxidant NAC; and 10 µM NF-κB inhibitor PDTC, as previously described (19).…”

Targeting mitochondrial metabolites and nucleic acids as an anti-inflammatory strategy

“…Another group of inhibitors target the ubiquinone binding site on SDH, and, among them, thenoyltrifluoroacetone (TTFA) has been used most frequently (Moreno et al, 2020). TTFA also reduce ROS production and proinflammatory cytokine production (Hop et al, 2017;Zhao et al, 2019). Of note, both DMM and TTFA have been shown to dampen severe inflammation caused by bacterial infection (Hop et al, 2017;Li et al, 2019).…”