Biochemistry, Physiology, and Pathophysiology of NADPH Oxidases in the Cardiovascular System

Lassègue, Bernard; Martín, Alejandra San; Griendling, Kathy K.

doi:10.1161/circresaha.111.243972

Cited by 686 publications

(790 citation statements)

References 401 publications

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“…Although their mechanism of action is still under investigation, p65‐GBPs have been shown to localize to vacuoles containing pathogens and play a role in transport of autophagic machinery, antimicrobial peptides, and NADPH oxidase (NOX) enzymes for assembly on phagosomal membranes 44, 45. Interestingly, both the phagocytic clearance of apoptotic cells, known as efferocytosis, and the production of reactive oxygen species by NOX enzymes are processes associated with the development of atherosclerosis 46, 47. Furthermore, similar to what happens during bacterial phagocytosis, efferocytosis was shown to induce an oxidative burst in macrophages in a NOX‐dependent fashion 48, 49.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling of Foam Cells Reveals Induction of Guanylate‐Binding Proteins Following Western Diet Acceleration of Atherosclerosis in the Absence of Global Changes in Inflammation

Goo

Son

Yechoor

et al. 2016

JAHA

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BackgroundFoam cells are central to two major pathogenic processes in atherogenesis: cholesterol buildup in arteries and inflammation. The main underlying cause of cholesterol deposition in arteries is hypercholesterolemia. This study aimed to assess, in vivo, whether elevated plasma cholesterol also alters the inflammatory balance of foam cells.Methods and ResultsApolipoprotein E–deficient mice were fed regular mouse chow through the study or were switched to a Western‐type diet (WD) 2 or 14 weeks before death. Consecutive sections of the aortic sinus were used for lesion quantification or to isolate RNA from foam cells by laser‐capture microdissection (LCM) for microarray and quantitative polymerase chain reaction analyses. WD feeding for 2 or 14 weeks significantly increased plasma cholesterol, but the size of atherosclerotic lesions increased only in the 14‐week WD group. Expression of more genes was affected in foam cells of mice under prolonged hypercholesterolemia than in mice fed WD for 2 weeks. However, most transcripts coding for inflammatory mediators remained unchanged in both WD groups. Among the main players in inflammatory or immune responses, chemokine (C‐X‐C motif) ligand 13 was induced in foam cells of mice under WD for 2 weeks. The interferon‐inducible GTPases, guanylate‐binding proteins (GBP)3 and GBP6, were induced in the 14‐week WD group, and other GBP family members were moderately increased.ConclusionsOur results indicate that acceleration of atherosclerosis by hypercholesterolemia is not linked to global changes in the inflammatory balance of foam cells. However, induction of GBPs uncovers a novel family of immune modulators with a potential role in atherogenesis.

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Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling of Foam Cells Reveals Induction of Guanylate‐Binding Proteins Following Western Diet Acceleration of Atherosclerosis in the Absence of Global Changes in Inflammation

Goo

Son

Yechoor

et al. 2016

JAHA

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“…These authors explain their results by an activating action of angiotensin II on an NADPH oxidase present in vascular tissue, of which p47 phox may be a component. 9 The resulting increase in superoxide production and concomitant decrease in nitric oxide levels (through dissipation by superoxide and production of tissue-damaging peroxynitrite) will result in hypertension. This process may be limited by the expression of p47 phox .…”

Section: Discussionmentioning

confidence: 99%

“…8 However, p47 phox is also expressed in non-phagocytic cells and may be involved in many other diseases, such as cardiovascular disorders. 9 Depending on the LCR in which the recombination event leading to the WBS deletion occurs, the NCF1 gene may or may not be deleted in WBS individuals. 1,3 Hemizygosity at the NCF1 locus may protect against hypertension in WBS 3 but as such has no effect on the susceptibility for microbial infections, because heterozygotes for AR 47 0 CGD caused by NCF1 mutations are asymptomatic.…”

Section: Introductionmentioning

confidence: 99%

Functional and genetic characterization of two extremely rare cases of Williams–Beuren Syndrome associated with chronic granulomatous disease

et al. 2013

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Brion 9,10 and Dirk Roos 8,10Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder with multi-systemic manifestations, caused by a heterozygous segmental deletion of 1.55-1.83 Mb at chromosomal band 7q11.23. The deletion can include the NCF1 gene that encodes the p47 phox protein, a component of the leukocyte NADPH oxidase enzyme, which is essential for the defense against microbial pathogens. It has been postulated that WBS patients with two functional NCF1 genes are more susceptible to occurrence of hypertension than WBS patients with only one functional NCF1 gene. We now describe two extremely rare WBS patients without any functional NCF1 gene, because of a mutation in NCF1 on the allele not carrying the NCF1-removing WBS deletion. These two patients suffer from chronic granulomatous disease with increased microbial infections in addition to WBS. Interestingly, one of these patients did suffer from hypertension, indicating that other factors than NADPH oxidase in vascular tissue may be involved in causing hypertension.

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“…In phagocytic cells, ROS play a role in host‐defense responses, and in nonphagocytic cells, ROS control cell differentiation, proliferation, apoptosis, and senescence 1, 2. In the vascular system, ROS regulate vasculogenesis, endothelial function, and vascular tone 3, 4.…”

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confidence: 99%

NADPH Oxidase 5 Is a Pro‐Contractile Nox Isoform and a Point of Cross‐Talk for Calcium and Redox Signaling‐Implications in Vascular Function

Montezano

Camargo

Persson

et al. 2018

JAHA

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BackgroundNADPH Oxidase 5 (Nox5) is a calcium‐sensitive superoxide‐generating Nox. It is present in lower forms and higher mammals, but not in rodents. Nox5 is expressed in vascular cells, but the functional significance remains elusive. Given that contraction is controlled by calcium and reactive oxygen species, both associated with Nox5, we questioned the role of Nox5 in pro‐contractile signaling and vascular function.Methods and ResultsTransgenic mice expressing human Nox5 in a vascular smooth muscle cell–specific manner (Nox5 mice) and Rhodnius prolixus, an arthropod model that expresses Nox5 endogenoulsy, were studied. Reactive oxygen species generation was increased systemically and in the vasculature and heart in Nox5 mice. In Nox5‐expressing mice, agonist‐induced vasoconstriction was exaggerated and endothelium‐dependent vasorelaxation was impaired. Vascular structural and mechanical properties were not influenced by Nox5. Vascular contractile responses in Nox5 mice were normalized by N‐acetylcysteine and inhibitors of calcium channels, calmodulin, and endoplasmic reticulum ryanodine receptors, but not by GKT137831 (Nox1/4 inhibitor). At the cellular level, vascular changes in Nox5 mice were associated with increased vascular smooth muscle cell [Ca2+]i, increased reactive oxygen species and nitrotyrosine levels, and hyperphosphorylation of pro‐contractile signaling molecules MLC20 (myosin light chain 20) and MYPT1 (myosin phosphatase target subunit 1). Blood pressure was similar in wild‐type and Nox5 mice. Nox5 did not amplify angiotensin II effects. In R. prolixus, gastrointestinal smooth muscle contraction was blunted by Nox5 silencing, but not by VAS2870 (Nox1/2/4 inhibitor).ConclusionsNox5 is a pro‐contractile Nox isoform important in redox‐sensitive contraction. This involves calcium‐calmodulin and endoplasmic reticulum–regulated mechanisms. Our findings define a novel function for vascular Nox5, linking calcium and reactive oxygen species to the pro‐contractile molecular machinery in vascular smooth muscle cells.

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Biochemistry, Physiology, and Pathophysiology of NADPH Oxidases in the Cardiovascular System

Cited by 686 publications

References 401 publications

Transcriptional Profiling of Foam Cells Reveals Induction of Guanylate‐Binding Proteins Following Western Diet Acceleration of Atherosclerosis in the Absence of Global Changes in Inflammation

Transcriptional Profiling of Foam Cells Reveals Induction of Guanylate‐Binding Proteins Following Western Diet Acceleration of Atherosclerosis in the Absence of Global Changes in Inflammation

Functional and genetic characterization of two extremely rare cases of Williams–Beuren Syndrome associated with chronic granulomatous disease

NADPH Oxidase 5 Is a Pro‐Contractile Nox Isoform and a Point of Cross‐Talk for Calcium and Redox Signaling‐Implications in Vascular Function

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