Peroxiredoxins as Potential Targets for Cardiovascular Disease

Se-Jin Jeong,Goo Taeg Oh,Jong-Gil Park

doi:10.3390/antiox10081244

Abstract

Increased oxidative stress (OS) is considered a common etiology in the pathogenesis of cardiovascular disease (CVD). Therefore, the precise regulation of reactive oxygen species (ROS) in cardiovascular cells is essential to maintain normal physiological functions. Numerous regulators of cellular homeostasis are reportedly influenced by ROS. Hydrogen peroxide (H2O2), as an endogenous ROS in aerobic cells, is a toxic substance that can induce OS. However, many studies conducted over the past two decades have provided substantial evidence that H2O2 acts as a diffusible intracellular signaling messenger. Antioxidant enzymes, including superoxide dismutases, catalase, glutathione peroxidases, and peroxiredoxins (Prdxs), maintain the balance of ROS levels against augmentation of ROS production during the pathogenesis of CVD. Especially, Prdxs are regulatory sensors of transduced intracellular signals. The intracellular abundance of Prdxs that specifically react with H2O2 act as regulatory proteins. In this review, we focus on the role of Prdxs in the regulation of ROS-induced pathological changes in the development of CVD.

Highlights

Mitochondria and enzyme systems involving nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) and xanthine oxidases are the main drivers of reactive oxygen species (ROS) production [15,16,17,18]
Monocytes recruited into the intima are differentiated into macrophages, which engulf oxidized LDLs (oxLDLs) through scavenger receptors and create inflammatory conditions in lesions by expressing various proinflammatory cytokines and the production of ROS and costimulatory molecules that activate other immune cells [23,24]
Oxidative Stress (OS), which is a common feature of Cardiovascular Disease (CVD), is thought to occur by an imbalance in the production and removal of ROS in cardiovascular cells

Summary

Introduction

CVD is caused by various heterogeneous pathophysiological mechanisms, increased OS is considered a potential common etiology [1,2,3]. Atherosclerosis is a chronic vascular inflammatory disease associated with the development of CVD, which is a leading cause of mortality and morbidity worldwide [20]. Monocytes recruited into the intima are differentiated into macrophages, which engulf oxLDLs through scavenger receptors and create inflammatory conditions in lesions by expressing various proinflammatory cytokines and the production of ROS and costimulatory molecules that activate other immune cells [23,24]. The development of AAA is associated with degraded plasticity of the tunica media with the activation of various proteases and inflammation caused by the accumulation of immune cells, angiogenesis, and necrosis [33]. NOX1 deficiency reportedly prevents Ang II-induced aortic dissection with an increased expression of the tissue inhibitor of metalloproteinase-1 in mice as compared with the wild-type controls [38]

ROS-Mediated Pathophysiological Changes in Vascular Cells

Overview of Prdxs

Conclusions and Future Perspectives