Peroxiredoxins as Potential Targets for Cardiovascular Disease

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.

Integrated bioinformatics and machine learning strategies reveal PRDX6 as the key ferroptosis-associated molecular biosignature of heart failure

“…Because of the core position of GPX4 in ferroptosis, the role of PRDX6 in ferroptosis is worth exploring (Lu et al 2019). Previous studies have shown that peroxidase can be used as a potential target for cardiovascular disease (Jeong et al 2021). A study in mice found that Peroxiredoxin 1 can prevent cardiac hypertrophy and HF caused by pressure overload by activating Nrf2/HO-1 signaling (Tang et al 2020).…”

Oxidative Stress in the Pathogenesis of Aorta Diseases as a Source of Potential Biomarkers and Therapeutic Targets, with a Particular Focus on Ascending Aorta Aneurysms

“…Particular attention has been also given to Prdxs, antioxidant enzymes involved in the regulation of OS and H 2 O 2 -mediated intracellular signalling by other research groups. Accordingly, studies have confirmed the impaired activity and expression of Prdxs, particularly of Prdx2, in patients affected by AsAA [ 49 ].…”

“…In contrast to CTGF activity and the mentioned enzymes above, and similarly to the actions mediated by Sirt3 [ 41 ], diverse intracellular enzymes, including superoxide dismutases, catalase, glutathione peroxidases and peroxiredoxins (Prdxs) (see Figure 1 and Table 2 ), have the role of maintaining precisely balanced ROS levels to reduce their eventual increase during the pathogenesis of diseases such as AsAA [ 49 ]. However, evidence has recently reported that the impaired function of these enzymes, as well as mitochondrial dysfunction, characterize patients affected by AsAA, as elegantly summarized by Portelli and co-workers [ 47 ].…”

Oxidative Stress in Cardiovascular Diseases

“…Currently, the implications of these thiol-based redox compounds on CVDs are being widely studied [55,58,59]. Endogenous Trx has the potential to decrease reperfusion-induced arrhythmia [60] and is a central mediator of cardiomyocyte growth [61].…”