The NAPDH oxidase (Nox) family is emerging as a key disease-related factor in vascular diseases, but currently its role in hypoxia-induced pulmonary remodelling in COPD remains unclear.Here we investigate the role of p22phox, a regulatory subunit of Nox, in COPD lungs, hypoxic pulmonary vasoconstriction (HPV), hypoxia-induced pulmonary vascular remodelling and pulmonary hypertension.In COPD, compared to control lungs, p22phox expression was significantly reduced.
The -930A/G polymorphism of the CYBA gene (that codes p22phox, a major component of the NADPH oxidase) has been associated with human hypertension and with a reduction in NADPH oxidase activity.
Furthermore the identification of genetic polymorphisms in the effectors involved in the pathophysiology of hypertension or in the response to anti-hypertensive drugs, such as the p22phox subunit of NADPH oxidase, alpha-adducin or adrenergic receptors, has promoted the prospective of both better understanding of hypertension and individualized strategies for its treatment.
In L-NAME treated rats, relative to Ad.Null or saline administration, Ad.CMV-hAM-4F2 (i) reduced augmented cardiomyocyte membrane protein oxidation and mRNA expression of pro-oxidant (p22phox) and anti-oxidant (SOD-3, GPx) genes; (ii) attenuated increased cardiomyocyte width and mRNA expression of hypertrophic (sk-alpha-actin) and cardio-endocrine (ANP) genes; (iii) did not attenuate hypertension.
Reactive oxygen species are implicated in the physiopathogenesis of salt-induced hypertension and the C242T polymorphism of the p22-phox gene has been associated with higher superoxide production.
According to the results of cross-sectional study, the tested polymorphism of the NADPH oxidase P22phox gene (rs4673) was found to be associated with the development of AH, indicating that the oxidative stress gene NADPH oxidase might be implicated in the pathogenesis of AH in subjects with type 2 diabetes.
Potential candidate genes in these regions that have been implicated in diabetic nephropathy and/or renal damage in models of hypertension include CYBA (or P22PHOX) (16q24), NOX1 (10q22), and NOX3 (6q25.1-q26).
These data suggest that the T allele of the CYBAC242T polymorphism may be used as a marker for adverse metabolic features in Brazilian subjects with systemic hypertension.
Polymorphisms in the p22phox gene promoter could determine susceptibility to NAD(P)H-mediated oxidative stress in humans and animals with hypertension.
The effect of p22(phox) -930A/G, A640G and C242T polymorphisms of NADPH oxidase on peripheral and central pressures in healthy, normotensive individuals.
Contribution of reactive oxygen species to the pathogenesis of left ventricular failure in Dahl salt-sensitive hypertensive rats: effects of angiotensin II blockade.
Potential candidate genes in these regions that have been implicated in diabetic nephropathy and/or renal damage in models of hypertension include CYBA (or P22PHOX) (16q24), NOX1 (10q22), and NOX3 (6q25.1-q26).