Expression of Concern: Molecular mechanism whereby paraoxonase‐2 regulates coagulation activation through endothelial tissue factor in rat haemorrhagic shock model

Abstract

We investigated the molecular mechanism of paraoxonase‐2 (PON‐2) in regulating blood coagulation activation in rats with haemorrhagic shock through endothelial tissue factor (TF). Thirty adult Sprague Dawley rats were randomly divided into three groups: healthy control group (group A), the haemorrhagic shock PON‐2 treatment group (group B), and the haemorrhagic shock group (group C). After the model was established, blood was withdrawn from the inferior vena cava of all rats. The difference in plasma thrombomodulin (TM) levels of the three groups was determined by Western blotting. The expression of transcription factors Egr‐1 and Sp1 was detected by Western blotting assays. reverse transcription‐polymerase chain Reaction (RT‐PCR) was used to determine the mRNA expression of t‐PA, PAI‐1, TM, and PON‐2 in the serum of three groups of rats. Endothelial TF was measured by enzyme linked immunosorbent assay (ELISA), and coagulation assay was used to detect the activity of coagulation factor VIII. Histopathological examination of the arteries of the rats was performed. The molecular mechanism of PON‐2 in regulating blood coagulation activation in haemorrhagic shock model rats by endothelial tissue factor was analysed. The expression of thrombin was determined by electrophoresis. Compared with the healthy control group, the expression of TM in groups B and C decreased, both 188.64 ± 12.47 and 137.48 ± 9.72, respectively, with a significant difference. The mRNA expression of TM and PON was determined by RT‐PCR. The mRNA expression of TM and PON in group B was 0.97 ± 0.07 and 1.14 ± 0.09, compared with the control group, and the mRNA expression of TM and PON in group C was 0.86 ± 0.38 and 1.12 ± 0.41, both of which increased, and there were significant differences. By measuring the expression of endothelial TF, the expression of TF in groups B and C was elevated to 12.69 ± 1.07 and 11.59 ± 0.87, with significant differences. The enzyme activities of PON‐2 in groups B and C, which were 110.34 ± 14.37 and 52.37 ± 8.06, respectively, were increased compared with the healthy control group and there were significant differences. PON‐2 regulates the activation of coagulation in rats with haemorrhagic shock by regulating the expression of endothelial tissue‐related genes such as plasma TM and endothelial TF under hypoxic and ischaemic conditions.

Human Paraoxonase-2 (PON2): Protein Functions and Modulation

“…Of relevance is a recent study suggesting a potential involvement of PON2 in the pathogenesis of venous thromboembolism in COVID-19 patients [125]. This is in line with previous but still recent studies showing that deregulated redox regulation in PON2 deficiency caused vascular inflammation and abnormalities in blood coagulation [126,127].…”

Insights into the role of paraoxonase 2 in human pathophysiology

“…Recent studies have shown that in endothelial cells, PON2 prevents systemic coagulation and inflammation by regulating the activity of tissue factors by a redox-dependent mechanism (Ebert et al 2018 ). In rats with hemorrhagic shock, it was found that under hypoxic and ischaemic conditions, PON2 regulates the expression of endothelial tissue-related genes such as plasma thrombomodulin transcription factors and endothelial tissue factor activating the mechanism of coagulation (Xu et al 2020 ).…”

miR‑let‑7c‑3p targeting on Egr‑1 contributes to the committed differentiation of leukemia cells into monocyte/macrophages

“…Egr-1 includes transactivation and repression regions, as well as three DNA-binding zinc finger regions that recognize GC-rich fragments of the promoter regions of target genes (51). Egr-1 has a wide range of functions, involving the control of synaptic plasticity, wound repair, inflammation, blood coagulation, pulmonary vascular permeability, growth and apoptosis of a number of cells (50,(52)(53)(54)(55)(56). Some findings suggest that Egr-1 can reverse the disease progression of acute myeloid leukemia by regulating changes in the downstream target genes c-myc and E2F1 (57).…”