Disruption of the NOX5 Gene Aggravates Atherosclerosis in Rabbits

Petheő, Gábor L.; Kerekes, Andrea; Mihálffy, Máté; Donkó, Ágnes; Bodrogi, L.; Skoda, Gabriella; Baráth, Mónika; Hoffmann, Orsolya Ivett; Szeles, Zsolt; Balázs, Bernadett; Sirokmány, Gábor; Fabian, Julia; Tóth, Zsuzsanna; Baksa, Ivett; Kacskovıcs, Imre; Hunyady, László; Hiripi, László; Bösze, Zsuzsanna; Geiszt, Miklós

doi:10.1161/circresaha.120.318611

Cited by 16 publications

(11 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most up-to-date-version is available at https://doi.org/10.1042/CS20210468 progression. Interesting results, by Petheo Gl et al [50], show that disruption of NOX5 gene accelerates atherosclerosis plaque formation in rabbits. These data and results from the present study demonstrate that NOX5 plays an important role in vascular homeostasis and that dysfunctional NOX5 activity, either inactivation or overactivation, negatively impacts vascular function [5,51].…”

Section: Lpc Stimulates Calcium Influxmentioning

confidence: 97%

Lysophosphatidylcholine induces oxidative stress in human endothelial cells via NOX5 activation – implications in atherosclerosis

et al. 2021

View full text Add to dashboard Cite

Objective: The mechanisms involved in NOX5 activation in atherosclerotic processes are not completely understood. This study tested the hypothesis that lysophosphatidylcholine (LPC), a proatherogenic component of oxLDL, induces endothelial calcium influx, which drives NOX5-dependent reactive oxygen species (ROS) production, oxidative stress, and endothelial cell dysfunction. Approach: Human aortic endothelial cells (HAEC) were stimulated with LPC (10-5 M, for different time points). Pharmacological inhibition of NOX5 (Melittin, 10-7 M) and NOX5 gene silencing (siRNA) were used to determine the role of NOX5-dependent ROS production in endothelial oxidative stress induced by LPC. ROS production was determined by lucigenin assay and electron paramagnetic spectroscopy (EPR), calcium transients by Fluo4 fluorimetry, and NOX5 activity and protein expression by pharmacological assays and immunoblotting, respectively. Results: LPC increased ROS generation in endothelial cells at short (15 min) and long (4 h) stimulation times. LPC-induced ROS was abolished by a selective NOX5 inhibitor and by NOX5 siRNA. NOX1/4 dual inhibition and selective NOX1 inhibition only decreased ROS generation at 4 h. LPC increased HAEC intracellular calcium, important for NOX5 activation, and this was blocked by nifedipine and thapsigargin. Bapta-AM, selective Ca2+ chelator, prevented LPC-induced ROS production. NOX5 knockdown decreased LPC-induced ICAM-1 mRNA expression and monocyte adhesion to endothelial cells. Conclusion: These results suggest that NOX5, by mechanisms linked to increased intracellular calcium, is key to early LPC-induced endothelial oxidative stress and pro-inflammatory processes. Since these are essential events in the formation and progression of atherosclerotic lesions, this study highlights an important role for NOX5 in atherosclerosis.

show abstract

Section: Lpc Stimulates Calcium Influxmentioning

confidence: 97%

Lysophosphatidylcholine induces oxidative stress in human endothelial cells via NOX5 activation – implications in atherosclerosis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The NOX5 gene is absent from rodent species and this has hampered our understanding of its role in atherosclerosis. A recent study using knock-in mice expressing human NOX5 in endothelial cells showed that NOX5 does not promote atherosclerosis [ 28 ], although deletion of NOX5 in New Zealand White rabbits significantly increased plaque development in the thoracic aorta, suggesting a protective role of NOX5 [ 29 ]. However, the role of NOX5 in human atherosclerosis remains unclear.…”

Section: Sources Of Ros In Atherosclerosismentioning

confidence: 99%

The Role of Oxidative Stress in Atherosclerosis

Batty

Bennett

2022

Cells

167

View full text Add to dashboard Cite

Atherosclerosis is a chronic inflammatory disease of the vascular system and is the leading cause of cardiovascular diseases worldwide. Excessive generation of reactive oxygen species (ROS) leads to a state of oxidative stress which is a major risk factor for the development and progression of atherosclerosis. ROS are important for maintaining vascular health through their potent signalling properties. However, ROS also activate pro-atherogenic processes such as inflammation, endothelial dysfunction and altered lipid metabolism. As such, considerable efforts have been made to identify and characterise sources of oxidative stress in blood vessels. Major enzymatic sources of vascular ROS include NADPH oxidases, xanthine oxidase, nitric oxide synthases and mitochondrial electron transport chains. The production of ROS is balanced by ROS-scavenging antioxidant systems which may become dysfunctional in disease, contributing to oxidative stress. Changes in the expression and function of ROS sources and antioxidants have been observed in human atherosclerosis while in vitro and in vivo animal models have provided mechanistic insight into their functions. There is considerable interest in utilising antioxidant molecules to balance vascular oxidative stress, yet clinical trials are yet to demonstrate any atheroprotective effects of these molecules. Here we will review the contribution of ROS and oxidative stress to atherosclerosis and will discuss potential strategies to ameliorate these aspects of the disease.

show abstract

“…NOX5 expression has been detected in lymphatic tissue, the testis, and blood vessels in humans [ 26 ]. Some studies showed that NOX5 contributes to vascular and kidney pathologies [ 26 ], but a recent study demonstrated a potential protective role of NOX5 against atherosclerosis in rabbits [ 27 ].…”

Section: Role Of Nadph Oxidasesmentioning

confidence: 99%

“…NOX5 contributes to coronary artery smooth muscle cell contraction, angiogenesis and atherosclerosis progression [ 35 , 36 ]. A recent study demonstrated a novel role for NOX5 in protecting against the progression of atherosclerosis [ 27 ]. NOX5-deficient young male rabbits consuming an atherogenic, high-fat feed developed significantly more plaques in the thoracic aorta compared to wild-type controls.…”

Section: Role Of Nadph Oxidasesmentioning

confidence: 99%

Inhibiting NADPH Oxidases to Target Vascular and Other Pathologies: An Update on Recent Experimental and Clinical Studies

et al. 2022

View full text Add to dashboard Cite

Reactive oxygen species (ROS) can be beneficial or harmful in health and disease. While low levels of ROS serve as signaling molecules to regulate vascular tone and the growth and proliferation of endothelial cells, elevated levels of ROS contribute to numerous pathologies, such as endothelial dysfunctions, colon cancer, and fibrosis. ROS and their cellular sources have been extensively studied as potential targets for clinical intervention. Whereas various ROS sources are important for different pathologies, four NADPH oxidases (NOX1, NOX2, NOX4, and NOX5) play a prominent role in homeostasis and disease. NOX1-generated ROS have been implicated in hypertension, suggesting that inhibition of NOX1 may be a promising therapeutic approach. NOX2 and NOX4 oxidases are of specific interest due to their role in producing extra- and intracellular hydrogen peroxide (H2O2). NOX4-released hydrogen peroxide activates NOX2, which in turn stimulates the release of mitochondrial ROS resulting in ROS-induced ROS release (RIRR) signaling. Increased ROS production from NOX5 contributes to atherosclerosis. This review aims to summarize recent findings on NOX enzymes and clinical trials inhibiting NADPH oxidases to target pathologies including diabetes, idiopathic pulmonary fibrosis (IPF), and primary biliary cholangitis (PBC).

show abstract

Disruption of the NOX5 Gene Aggravates Atherosclerosis in Rabbits

Cited by 16 publications

References 5 publications

Lysophosphatidylcholine induces oxidative stress in human endothelial cells via NOX5 activation – implications in atherosclerosis

Lysophosphatidylcholine induces oxidative stress in human endothelial cells via NOX5 activation – implications in atherosclerosis

The Role of Oxidative Stress in Atherosclerosis

Inhibiting NADPH Oxidases to Target Vascular and Other Pathologies: An Update on Recent Experimental and Clinical Studies

Contact Info

Product

Resources

About