A M Shah

..CONCLUSIONS: Nox4D is a nuclear-localized and functionally active splice variant of Nox4 that may have important pathophysiologic effects through modulation of nuclear signaling and DNA damage...

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..Increased RAAS activation may drive age-related cardiac remodeling through the activation of Nox2 NADPH oxidase and subsequent increases in MMP activation, fibrosis and cardiomyocyte hypertrophy...

..A better understanding of this complex regulatory system may allow the development of more specific therapeutic strategies for heart diseases...

..In this article, we review our current understanding of the roles of NOX enzymes in several common cardiovascular disease states, with a focus on data from genetic studies and clinical data where available...

..These results indicate that an increase in endothelial Nox2 levels contributes to angiotensin II-induced endothelial dysfunction, vascular remodeling and hypertension...

..abstract:..

..Genome-wide expression patterns in physiological cardiac hypertrophy. Co-expression patterns in physiological cardiac hypertrophy..

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..The balance between beneficial and deleterious effects of NO is of key importance with respect to its pathophysiological role...

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..The IVC segment approach is a clinically acceptable approach to liver gene therapy. However, it is less effective in pigs than in rodents, possibly because of larger liver size or a less compliant connective tissue framework...

..The complexity of regulation of NADPH oxidases in these conditions may provide the possibility of targeted therapeutic manipulation in a cell-, tissue- and/or pathway-specific manner at appropriate points in the disease process...

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..In conclusion, diabetic hearts exhibit markedly abnormal post-hypoxic relaxation, which is attributable to both ROS and NO derived from iNOS...

..We compared the involvement of Nox2 versus Nox4 in redox-sensitive protein kinase activation after agonist stimulation...

..These data suggest a differential response of the cardiac Nox isoforms, gp91phox and Nox4, to Ang II versus pressure overload...

..Because this study was performed in patients with moderate heart failure, whether the findings apply to subjects with more severe heart failure requires further investigation...

..These are the first data to potentially link increased NADPH oxidase-derived ROS with a defect in cardiac contractile function in a pathological setting...

..Abstracts of all references were screened before selecting those relevant to this review...

..g., the Frank-Starling mechanism, neurohumoral influences, the effects of heart rate, coronary perfusion and load. A better understanding of its physiological and pathophysiological roles may lead to novel therapeutic strategies...

..Like the neutrophil enzyme, the endothelial oxidase is preferentially NADPH- rather than NADH-dependent. NADH-dependent O(2)(-) production appears to be an artefact related to the use of lucigenin doses > or =50 micromol/l...

..CONCLUSIONS: A gp91(phox)-containing NADPH oxidase plays an important role in the development of angiotensin II-induced cardiac hypertrophy, independent of changes in blood pressure...

..This study was designed to investigate in vivo mechanisms involved in TRPV1-mediated peripheral vasodilatation...

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..Such a mechanism could have important implications for the regulation of oxygen supply-demand balance in the heart and be relevant to conditions such as myocardial hibernation...

..In the present paper, we review the structure and mechanisms of activation of NADPH oxidases and consider their involvement in redox signalling, focusing mainly on the cardiovascular system...

..CONCLUSIONS: Tumor necrosis factor activates p38-MAPK in the intact heart and in isolated cardiac myocytes through MKK3. This activation likely contributes to the early cardiodepressant action of TNFalpha...

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..These data suggest divergent downstream effects of Nox2 on different components of the overall response to pressure overload...

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..Vagal blockade with atropine, and the use of Ringer's solution to prevent electrolyte disturbances, did not ameliorate this picture...

..Among these measurements, WHR was the only independent predictor of FMD (r2 = 0.30; p = 0.0001). CONCLUSIONS: WHR is an important marker of endothelial dysfunction in healthy people across a wide range of body fatness...

..To explore the relation between non-invasive measures of cardiac function and sudden cardiac death, as well as the development and utility of an index integrating these variables to identify patients at increased risk of this mode of death...

..Thus, mouse coronary microvascular endothelial cells express both eNOS and NADPH oxidase, interactions between which may play a role in endothelial cell pathophysiology...

..Mitral stenosis in pregnancy and its management in pregnancy are briefly discussed...

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..We also identified more distal, upstream regions which act to repress significantly expression from the Nox1 promoter...

..We therefore compared the IR technique against cine fast low shot angle (cine-FLASH) for the quantification of MI size in mice at 7T in vivo...

..Our results also have wider relevance to the use of nonspecific antioxidant approaches in cardiac disease and may provide an explanation for the failure of such strategies in many settings...

..The aim of this study was to determine whether modulation of PP2A and thus cTnI phosphorylation could improve sepsis-induced contractile dysfunction...

..1+/-5.4 to 31.3+/-3.9 arbitrary units, P<0.01). In conclusion, acute elevation of FFA in healthy men increases arterial blood pressure and reduces vascular resistance. These haemodynamic changes could be clinically relevant...

..Understanding NADPH oxidase activation and regulation, and their downstream effectors, could help to develop novel therapeutic targets...

..Mortality in patients with mild to moderate chronic heart failure remains high. At present there is no easy way of identifying patients within this population at increased risk of death in the medium to long term...

..This article reviews current knowledge of the nonphagocyte-NADPH oxidases at both structural and biochemical levels and discusses the possible role of these enzymes in the pathophysiology of diabetic nephropathy...

..The aim of this study was to explore the value of noninvasive predictors of death/mode of death in ambulant outpatients with chronic heart failure (HF)...

..4-fold; P < 0.01) in troponin I phosphorylation compared to control, untreated hearts. These results suggest that the reduction in myofilament Ca(2+) responsiveness produced by DEA/NO results from phosphorylation of troponin I by PKG...

..The p47phox subunit plays an important role in Ang II-induced oxidase activation, but its role in basal oxidase activity and vascular function is unclear...

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..PKC-dependent activation of a NOX-2-containing NADPH oxidase is pivotally involved in early ischemic PC. However, adenosine receptor activation can trigger a ROS and NOX-2 independent PC pathway...

..CONCLUSIONS: These data uncover a role of endogenous endothelin-1 in the maintenance of basal vasomotor tone in patients with angiographically normal coronary arteries...

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..We hypothesised that inspiratory muscle endurance, expressed as a function of endurance time (Tlim) adjusted for inspiratory muscle load and inspiratory muscle capacity, would be reduced in CHF...

..We then focus on the potential factors responsible for endothelial dysfunction in obesity and possible therapeutic interventions targetted at these abnormalities...

..A better understanding of redox signalling mechanisms may enable the development of new targeted therapeutic strategies rather than the non-specific antioxidant approaches that have to date been disappointing in clinical trials...

..The increased binding between p47phox and TRAF4 that occurs after p47phox phosphorylation could serve to spatially confine ROS generation from NADPH oxidase and subsequent MAPK activation and cell surface ICAM-1 expression in EC...

..There is significant strain-dependent variation in coronary and aortic vascular responsiveness in mice, which may reflect differences in the balance between NO and superoxide generation...

..These data show that endothelial cell p47(phox) is critical in the upregulation of NADPH oxidase activity by PMA and TNFalpha...

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..These data could suggest new ways of targeting redox pathways for the prevention and treatment of adverse cardiac remodeling...

..This review provides an overview of NADPH oxidase structure and regulation in endothelial cells and their role in pathophysiology, focussing particularly on endothelial activation...

..The sequence identity between mouse and human NOX-2S strongly implies conservation in function and possibly a role for NOX-2S in the regulation of NADPH oxidase activity...

..Here, we investigated the in vivo effects of an nNOS-selective inhibitor, S-methyl-L-thiocitrulline (SMTC), on the human coronary circulation and on flow-mediated dilatation in the forearm...

..However, the effects of early-glycated proteins, such as glycated serum albumin (Gly-BSA), are poorly defined. In this study, we investigated the effects of Gly-BSA on reactive oxygen species (ROS) production by cardiomyocytes...

..A better understanding of the roles of this complex enzyme family may define novel therapeutic targets for the prevention of heart failure...

..Experimental study of cardiac function in the diabetic heart has focussed mostly on models of Type I diabetes. We studied cardiac function in the Goto-Kakizaki (GK) rat, an inbred model of spontaneous non-obese, Type II diabetes...

..These results suggest that aldosterone-dependent activation of a Nox2-containing NADPH oxidase contributes to the profibrotic effect of AngII in the heart as well as the fibrosis seen in mineralocorticoid-dependent hypertension...

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..Our data suggest that IGFBP-1 plays an important and potentially beneficial role in regulating metabolic and vascular homeostasis...

..In this article, we review the current understanding of this important but complex field, focussing particularly on contractile function and on recent advances in knowledge regarding the autocrine functions of nNOS-derived NO...

..There is good evidence that nitric oxide has important autocrine/paracrine effects in the myocardium, serving to optimise and fine tune cardiac function..

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..To examine the clinical outcome of percutaneous coronary intervention where the procedure was complicated by vessel perforation...

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..The increase in NADPH oxidase activity in the failing heart may be important in the pathophysiology of cardiac dysfunction by contributing to increased oxidative stress...

..This article reviews current knowledge regarding the role of NADPH oxidases in cardiomyocyte function in health and disease...

..These data indicate that angiotensin II-stimulated endothelial NADPH oxidase activity is regulated through serine phosphorylation of p47(phox) and its enhanced binding to p22(phox)...

..2 (1.2)% versus 8.3 (1.5)%, p=0.9. ACE inhibition had no effect on insulin, lipids or circulating cytokines. In healthy obese humans, despite a significant reduction in blood pressure, ACE inhibition had no effect on FMD...

..These results indicate that, in contrast to the neutrophil enzyme, a substantial proportion of the NADPH oxidase in unstimulated endothelial cells exists as a preassembled intracellular complex associated with the cytoskeleton...

..Insulin resistance is associated with endothelial dysfunction; however, the mechanistic relationship between these abnormalities and the role of impaired endothelial insulin signaling versus global insulin resistance remains unclear...

..Its action is not nitric oxide or endothelial-dependent. Markers of body fat did not correlate with leptin-mediated vasodilatation, raising the intriguing possibility of selective resistance to leptin's actions...

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..These findings underscore the importance of early intervention in insulin-resistant states, where glucose homeostasis may be normal but substantial abnormalities of the vascular effects of insulin may already be present...

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..Recent studies indicate that it generates predominantly hydrogen peroxide (H(2)O(2)), but its role in vivo remains unclear...

..To validate a novel method for assessment of coronary endothelium-dependent microvascular function and compare this index with the adenosine-derived coronary flow reserve (CFR)...

..Cardiac troponins are highly sensitive and specific markers of myocardial cell injury. We wished to determine the clinical relevance of raised troponins in the absence of significant angiographic coronary artery disease...

..If confirmed, these data would suggest that independently targeting different members of the NOX family may hold the potential for therapeutic intervention in the treatment of cardiac disease...

..Our results provide evidence of increased nNOS-derived NO in the failing human heart. Such altered regulation may be important in the pathophysiology of cardiac dysfunction in human congestive heart failure...

..This review focuses on recent advances in understanding the mechanisms of cTnI modification by these kinases and the consequent functional effects both under physiological conditions and in pathophysiological settings...

..These data suggest that the Nox2-containing reduced nicotinamide-adenine dinucleotide phosphate oxidase contributes significantly to the processes underlying adverse cardiac remodeling and contractile dysfunction post-MI...

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..We investigated the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in endothelial dysfunction in human heart failure...

..This may contribute to the lower NO bioavailability and higher incidence of cardiovascular disease seen in black Africans...

..05). Thus, inhibition of NADPH oxidase-derived ROS overproduction improves the angiogenic and vasculogenic processes and restores postischemic neovascularization in type 1 diabetic mice...