A novel pathway of NADPH oxidase/vascular peroxidase 1 in mediating oxidative injury following ischemia–reperfusion

Abstract

Vascular peroxidase 1 (VPO1) can utilize reactive oxygen species (ROS) generated from NADPH oxidase (NOX) to catalyze peroxidative reactions. This study was performed to identify a novel pathway of NOX/VPO1 in mediating the oxidative injury following myocardial ischemia reperfusion (IR). In a rat model of myocardial IR, the infarct size, serum creatine kinase (CK) activity, apoptosis, NOX activity, NOX2 and VPO1 expression were measured. In a cell (rat heart-derived H9c2 cells) model of hypoxia/reoxygenation (HR), the apoptosis, NOX activity, NOX2 and VPO1 expression, and H(2)O(2) and HOCl levels were examined. In vivo, IR caused 54.8 ± 1.7 % infarct size in myocardium accompanied by elevated activities of CK, caspase-3 and NOX, up-regulated VPO1 expression and high numbers of myocardial apoptotic cells; these effects were attenuated by pretreatment with the inhibitor of NOX. In vitro, inhibition of NOX or silencing of NOX2 or VPO1 expression significantly suppressed HR-induced cellular apoptosis concomitantly with decreased HOCl production. Inhibition of NOX or silencing of NOX2 led to a decrease in H(2)O(2) production accompanied by a decrease in VPO1 expression and HOCl production. However, silencing of VPO1 expression did not affect NOX2 expression and H(2)O(2) production. H(2)O(2)-induced VPO1 expression was partially reversed by JNK or p38 MAPK inhibitor. Our results demonstrate a novel pathway of NOX2/VPO1 in myocardium, where VPO1 coordinates with NOX2 and amplifies the role of NOX-derived ROS in oxidative injury following IR.

VPO1 Modulates Vascular Smooth Muscle Cell Phenotypic Switch by Activating Extracellular Signal‐regulated Kinase 1/2 (ERK 1/2) in Abdominal Aortic Aneurysms

“…In addition, MPO is only expressed in neutrophils and monocytes under inflammatory response and VPO1 is highly expressed in cells of the cardiovascular system,10 therefore, it may be more significant to explore the role of VPO1 in AAA development. Our previous studies demonstrated that VPO1/HOCl pathway‐mediated oxidative stress contributed to hypoxia‐induced pulmonary vascular remodeling, angiotensin II‐induced VSMC proliferation and myocardial ischemia‐reperfusion injury 8, 11, 19. In this study, we find that VPO1 and 3‐Cl‐tyr (a product of HOCl reacting with tyrosine residues) are significantly increased in human aneurysm tissues compared with healthy aortic tissues.…”

“…Our group previously reported VPO1 uses H 2 O 2 to generate HOCl, a highly reactive oxidant, and enhances oxidative stress in the cardiovascular system 18, 19. To study the effect of HOCl generated by VPO1, we examined the levels of 3‐Cl‐tyr, a product of HOCl reaction with tyrosine, by Western blot after H 2 O 2 treatment in cells with VPO1 depletion.…”

Cardioprotective Effects of Combined Therapy with Hyperbaric Oxygen and Diltiazem Pretreatment on Myocardial Ischemia-Reperfusion Injury in Rats

“…The oxidative stress events are recognized to participate in MIRI processes, ultimately leading to cell apoptosis and death, cell damage, and mitochondrial dysfunction [3,37]. Following a period of ischemia, re-establishment of the oxygen supply will produce an excessive amount of ROS, which triggers oxidative stress and then induces MIRI [38,39].…”

Activation of a7 Nicotinic Acetylcholine Receptor Protects Against Oxidant Stress Damage Through Reducing Vascular Peroxidase-1 in a JNK Signaling-Dependent Manner in Endothelial Cells

“…VPO-1 is a novel family member of peroxidases identified in cardiovascular system in 2008 [39]. VPO-1 is highly expressed in cardiomyocytes, endothelial cells and vascular smooth muscle cells [40,41,42], and thereby referred to vascular peroxidase (VPO). It is a glycosylated heme-peroxidase that is actively secreted into circulating plasma by vascular endothelial cells [39].…”