Abstract
Peroxiredoxin 2 (PRDX2), an inhibitor of reactive oxygen species (ROS), is potentially involved in the progression of atherosclerosis (AS). The aim of this study was to explore the role and mechanism of PRDX2 in AS. The expression of PRDX2 was evaluated in 14 human carotid artery tissues with or without AS. The results showed that the positive reaction of PRDX2 was observed in the carotid artery vascular smooth muscle cells (CAVSMCs). To assess the mechanism by which PRDX2 may function in AS, the CAVSMCs were transfected with pEX4-PRDX2 and si-PRDX2. The catalase, hydrogen peroxide (H2O2) scavenger, was used to further confirm that PRDX2-induced inhibitory effects might be mediated through reducing ROS levels. Phenotype alteration and functional testing included transcription testing, immunostaining, and expression studies. The drug of MAPK signaling pathway inhibitors SB203580, SP600125, and PD98059 was used to evaluate the underlying mechanism. In this study, we found that the protein level of PRDX2 and the level of H2O2 were higher in the human AS carotid artery tissues than in the normal carotid artery tissues, accompanied with the activation of MAPK signaling pathway. The up-regulation of PRDX2 in the CAVSMCs significantly decreased the expression of ROS, collagen type I (COL I), collagen type III (COL III), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) and inhibited the proliferation, migration, and transformation of the CAVSMCs. The up-regulation of PRDX2 reversed the effect of the CAVSMCs treated with tumor necrosis factor-α (TNF-α). In addition, PRDX2 down-regulation promoted the protein levels of p-p38, p-JNK, and p-ERK, which was confirmed in relevant MAPK inhibitor treatment experiments. Our results suggest a protective role of PRDX2, as a scavenger of ROS, in AS progression through inhibiting the VSMC phenotype alteration and function via MAPK signaling pathway.
Highlights
Peroxiredoxin (PRDX) is an antioxidant protease containing important catalytic cysteine residues, which can be used to remove hydrogen peroxide (H2O2), lipid H2O2, and peroxynitrite [1, 2]
The Western blot assays indicated that the expression of Peroxiredoxin 2 (PRDX2), collagen type I (COL I), collagen type III (COL III), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) was significantly higher in the tumor necrosis factor-α (TNF-α)-treated group than in the control group, which was reversed by catalase treatment (Figure 2H)
The protein expression of PRDX2 and the concentration of H2O2 were markedly increased in the human carotid AS tissue compared with the normal human carotid artery tissue, which suggested that both of them were involved in the progression of AS
Summary
Peroxiredoxin (PRDX) is an antioxidant protease containing important catalytic cysteine residues, which can be used to remove hydrogen peroxide (H2O2), lipid H2O2, and peroxynitrite [1, 2]. There are six subtypes of the PRDX family in mammals, which are generally divided into 1-cys and 2-cys according to the number of cysteine residues, among which PRDX 1–5 belong to 2-cys subtype, and PRDX 6 belongs to 1cys subtype [3]. PRDX2 expression was more pronounced in the endothelial cells and immune cells in atheroid-prone areas and plaques [10]. It remains unclear the mechanism underlying the role of PRDX2 in the development of AS
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