Oxidative stress and cardiovascular risk: the role of vascular NAD(P)H oxidase and its genetic variants

Soccio, Manola; Toniato, E; Evangelista, Virgilio; Carluccio, Maria Annunziata; Caterina, Raffaele De

doi:10.1111/j.1365-2362.2005.01500.x

Cited by 79 publications

(47 citation statements)

References 65 publications

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“…More detailed analysis of the roles of Ki-ras2A signaling in VSMC proliferation, senescence and phenotypic changes could contribute to further understanding of the pathogenesis of vascular remodeling. It has been suggested that oxidative stress plays a role in the onset and pathogenesis of cardiovascular diseases [37], involving cellular senescence [17,18] and activation of Ras [38]. Moreover, accumulating evidence suggests that Ang II and Aldo mediate oxidative stress by activating NADPH oxidase, which results in superoxide production [13,14,16].…”

Section: Discussionmentioning

confidence: 99%

Cross-talk between aldosterone and angiotensin II in vascular smooth muscle cell senescence

Min

Mogi

Iwanami

et al. 2007

Cardiovascular Research

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Objective: Our aim was to examine the possible cross-talk of angiotensin II (Ang II) and aldosterone (Aldo) in the regulation of vascular cell senescence in cultured vascular smooth muscle cells (VSMC). Methods: VSMC were prepared from thoracic aorta of adult male Sprague-Dawley rats. Cellular senescence was evaluated by senescenceassociated β-galactosidase (SA-β-gal) staining and expression of p21, p53, p16, and p27. Oxidative stress was determined by measuring NADPH oxidase activity and superoxide production. Signal transduction was examined by immunoblot analysis with or without RNA interference methods. Results: Persistent Ang II (100 nM) stimulation increased SA-β-gal-stained VSMC and enhanced expression of p21, p53, p16, p27 and Kiras2A. These effects of Ang II were markedly inhibited by treatment with a selective AT 1 receptor blocker, valsartan, but partially attenuated by a mineralocorticoid receptor antagonist, spironolactone. The culture medium of VSMC treated with Ang II (100 nM) showed a timedependent increase in Aldo concentration, which increased senescent VSMC. Antioxidant, N-acetyl-L-cysteine or superoxide dismutase attenuated Ang II-or Aldo-induced VSMC senescence and Ki-ras2A expression. A lower dose combination of Ang II (100 pM) and Aldo (1 pM) significantly enhanced SA-β-gal-stained VSMC with increases in expression of p21, p53, p16, p27 and Ki-ras2A, oxidative stress, and activity of transcription factors such as NF-κB, AP-1, whereas Ang II or Aldo alone at these doses did not affect these parameters. Kiras2A-siRNA treatment attenuated senescent VSMC, expression of p21, p53, p16 and p27, oxidative stress induced by Ang II or a lower dose combination of Ang II and Aldo. Conclusion: These results suggest that Ang II and Aldo exert cross-talk in VSMC senescence with involvement of oxidative stress and Kiras2A, and could provide a therapeutic benefit for age-related vascular disorders by blockade of both Ang II and Aldo.

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Section: Discussionmentioning

confidence: 99%

Cross-talk between aldosterone and angiotensin II in vascular smooth muscle cell senescence

Min

Mogi

Iwanami

et al. 2007

Cardiovascular Research

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“…Although polymorphisms that affect key pro-and antioxidant enzymes might alter the susceptibility to oxidative stress-mediated injury, the use of genetic epidemiology for the study of oxidative stress-related genes has received little attention in ARF (10,11). Whereas a number of polymorphisms of oxidant stress-related genes might be functionally relevant in human disease (29), we chose to evaluate the genetic variants of two key leukocyte-and endothelium-associated enzymes: NADPH oxidase and catalase. Given its importance in generating superoxide during the respiratory burst of neutrophils, one might anticipate that polymorphisms that disrupt the function of NADPH oxidase would alter oxidative stress-mediated injury in conditions such as ARF.…”

Section: Discussionmentioning

confidence: 99%

NADPH Oxidase p22phox and Catalase Gene Variants Are Associated with Biomarkers of Oxidative Stress and Adverse Outcomes in Acute Renal Failure

Perianayagam

Liangos

Kolyada

et al. 2007

Journal of the American Society of Nephrology

123

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Reactive oxygen species are important mediators of injury in acute renal failure (ARF). Although polymorphisms that affect key pro-and antioxidant enzymes might alter the susceptibility to oxidative stress-mediated injury, the use of genetic epidemiology for the study of oxidative stress-related genes has received little attention in ARF. The relationship of single-nucleotide polymorphisms in the coding region (C to T substitution at position ؉242) of the pro-oxidant enzyme NADPH oxidase p22phox subunit gene and in the promoter region (C to T substitution at position ؊262) of the antioxidant enzyme catalase gene to adverse clinical outcomes was evaluated prospectively in a cohort of 200 hospitalized patients with established ARF of mixed cause and severity. Genomic DNA was extracted from peripheral blood leukocytes and analyzed with a restriction fragment length polymorphism PCR method. Genotype-phenotype associations were characterized by measuring circulating nitrotyrosine and catalase activity. Observed and expected genotype frequencies were not significantly different, and overall baseline characteristics were not significantly different according to the various genotype groups. A genotype-phenotype association was demonstrable between the NADPH oxidase p22phox genotypes and plasma nitrotyrosine level (P ‫؍‬ 0.06), as well as between the catalase genotypes and whole-blood catalase activity (P < 0.001). Compared with the NADPH oxidase p22phox CC genotype group, the T-allele group had a higher cumulative probability of remaining hospitalized (P ‫؍‬ 0.03). Compared with the NADPH oxidase p22phox CC genotype, the T-allele carrier state was associated with 2.1-fold higher odds for dialysis requirement or hospital death (P ‫؍‬ 0.01). This association persisted with 2.0-to 2.2-fold higher odds for this composite outcome after adjustment for race; gender; age; and the Acute Physiology and Chronic Health Evaluation II score (P ‫؍‬ 0.03), the Multiple Organ Failure score (P ‫؍‬ 0.01), or presence of sepsis (P ‫؍‬ 0.02). The polymorphism in the gene that encodes the NADPH oxidase p22phox subunit at position ؉242 is associated with dialysis requirement or hospital death among patients with ARF. Larger studies are needed to confirm these relationships.

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“…Potentially relevant SNPs in the p22 phox gene include an Ala174Val polymorphism (33% allelic frequency) and a His72Tyr polymorphism (29% allelic frequency) (217,821). The latter polymorphism is caused by a C to T substitution and is often also referred to as the C242T polymorphism (693).…”

Section: Subunits and Regulatory Proteinsmentioning

confidence: 99%

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

Bedard¹,

Krause²

2007

Physiological Reviews

5,931

117

5,778

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For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phagocyte NADPH oxidase were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with the phagocyte NADPH oxidase itself (NOX2/gp91phox), the homologs are now referred to as the NOX family of NADPH oxidases. These enzymes share the capacity to transport electrons across the plasma membrane and to generate superoxide and other downstream reactive oxygen species (ROS). Activation mechanisms and tissue distribution of the different members of the family are markedly different. The physiological functions of NOX family enzymes include host defense, posttranlational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. NOX enzymes also contribute to a wide range of pathological processes. NOX deficiency may lead to immunosuppresion, lack of otoconogenesis, or hypothyroidism. Increased NOX actvity also contributes to a large number or pathologies, in particular cardiovascular diseases and neurodegeneration. This review summarizes the current state of knowledge of the functions of NOX enzymes in physiology and pathology.

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Oxidative stress and cardiovascular risk: the role of vascular NAD(P)H oxidase and its genetic variants

Cited by 79 publications

References 65 publications

Cross-talk between aldosterone and angiotensin II in vascular smooth muscle cell senescence

Cross-talk between aldosterone and angiotensin II in vascular smooth muscle cell senescence

NADPH Oxidase p22phox and Catalase Gene Variants Are Associated with Biomarkers of Oxidative Stress and Adverse Outcomes in Acute Renal Failure

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

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