Ralf P Brandes

..Thus, the vascular NADPH oxidases play an important role in mediating the signal transduction cascade of pro-arteriosclerotic stimuli...

..The soluble epoxide hydrolase (sEH) metabolizes EETs to their less active diols. We hypothesized that knockout and inhibition of sEH prevents neointima formation in hyperlipidemic ApoE(-/-) mice...

..The function of Nox4, a source of vascular H(2)O(2), is unknown. Other Nox proteins were identified as mediators of endothelial dysfunction...

..We hypothesized that NADPH oxidases mediate blood-brain barrier (BBB) disruption and contribute to tissue damage in ischemia/reperfusion...

..Collectively, the first in vivo data of the kidney do not support the view that Nox4 is a main driver of renal disease. It rather appears that under specific conditions Nox4 may even slightly limit injury and disease progression...

..Thus, sEH-inhibition failed to elicit protective effects in the 5/6-Nx model and showed a tendency to aggravate the disease. These effects might be consequence of a shift of arachidonic acid metabolism into the lipoxygenase pathway...

..Ex vivo, SP600125 blocked HGF-induced migration and tube formation. We conclude that HGF-induced mobilization of EPCs and the proangiogenic effects of the growth factor require a Nox2-dependent ROS-mediated activation of Jak2 and Jnk...

..We determined in human and mouse preadipocytes whether Nox proteins contribute to ROS formation and differentiation in response to insulin...

..controlling blood pressure and vascular function in angiotensin II-dependent models of hypertension. ecSOD is expressed in such an abundance that even in situations of high oxidative stress no relative lack of enzyme activity occurs...

..Thus, the very N-terminal part of Nox proteins determines subcellular localization and the ROS type released, whereas the cytosolic tail regulates activity...

..Therefore, tungsten, potentially via the inhibition of XO, prevents the development of endothelial dysfunction and atherosclerosis in ApoE(-/-) mice on WD...

..We studied the function of ecSOD in high-volume hypertension induced by the 1-kidney-1-clip model in wild-type, ecSOD-/- mice, and endothelial nitric oxide synthase (eNOS)-/- mice...

..These observations indicate that apocynin predominantly acts as an antioxidant in endothelial cells and vascular smooth muscle cells and should not be used as an NADPH oxidase inhibitor in vascular systems...

..Direct vasodilatation of resistance arteries in skeletal muscles does not appear to contribute to the antihypertensive effects of sEH inhibition in mice...

..Thus, H(2)O(2) formation is an intrinsic property of Nox4 that involves its E-loop. The structure of the E-loop may hinder O(2)(·-) egress and/or provide a source for protons, allowing dismutation to form H(2)O(2)...

..The role of hypoxia and reactive oxygen species (ROS) in mobilization and function of these cells is incompletely understood...

..In conclusion, these data indicate that Noxa1 replaces p67phox in VSMC and plays a central role in the activation of the NADPH oxidase in the vascular wall...

..We assessed whether the uncoupling of eNOS was associated with alterations in eNOS phosphorylation and/or the assembly of the eNOS signaling complex...

..Obesity is associated with hyperleptinemia but it is not clear whether leptin protects vascular function or promotes dysfunction. We therefore studied the consequences of hyperleptinemia in lean mice...

..Aging is also associated with a reduction in the regenerative capacity of the endothelium and endothelial senescence, which is characterized by an increased rate of endothelial cell apoptosis...

..Basic fibroblast growth factor (bFGF) stimulates vascular smooth muscle cell (SMC) migration. We determined whether bFGF increases SMC reactive oxygen-species (ROS) and studied the role of ROS for SMC migration...

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..This review focuses on the specific role of different NADPH oxidase isoforms in vascular physiology and their potential contributions to vascular diseases...

..Because EETs have antiinflammatory properties, we determined whether or not inhibition of sEH attenuates disease development in the monocrotaline model of pulmonary hypertension in rats...

..Thus, ACE is involved in outside-in signaling in endothelial cells and "ACE signaling" may be an important cellular mechanism contributing to the beneficial effects of ACE inhibitors...

..The underlying mechanism involves activation of a gp91phox-containing NADPH oxidase by Rac-1 and the subsequent scavenging of endothelium-derived NO by superoxide anions generated from this enzyme...

..Recently, significant progress has been made in the understanding of differences among the Nox proteins...

..Our results suggest that Nox4 essentially contributes to nociceptive processing in neuropathic pain states. Accordingly, inhibition of Nox4 may provide a novel therapeutic modality for the treatment of neuropathic pain...

..Consequently, selective pharmacologic inhibition of Nox proteins has a potential to interfere with cardiovascular disease initiation and progression...

..Obviously, there exists a fine-tuned crosstalk between NO and ROS generating systems in the course of inflammatory diseases...

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..Finally, the contribution of NADPH oxidases to the predominant cardiovascular diseases will be discussed...

..This article reviews the components of the NADPH oxidases in leukocytes and vascular tissue. Emphasis is put on the activation of the oxidases, including upstream signalling events and molecular modes of interaction between the subunits...

..Emphasis will be put on most recent technical innovations and the shortcomings associated with current techniques...

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..We conclude that p47phox is important for vascular ROS production and redox-modulated signaling and gene expression in VSMC...

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..Given that active TF promotes thrombin formation, the NADPH oxidase may play a crucial role in perpetuating the thrombogenic cycle in the injured vessel wall...

..These results suggest that PDI closely associates with NAD(P)H oxidase and acts as a novel redox-sensitive regulatory protein of such enzyme complex, potentially affecting subunit traffic/assembling...

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..We conclude that NADPH oxidase is expressed in skeletal muscle precursor cells and that its activity plays an important role in promoting proliferation of these cells...

..Our goal was to demonstrate that microparticles (MPs) are the endogenous signal leading to neovessel formation through CD40 ligation in human atherosclerotic plaques...

..This suggests a crosstalk between mitochondrial and Nox-derived ROS with distinct mechanistic effects and sites for pharmacological intervention...

..Taken together, EPCs reveal a higher expression of antioxidative enzymes and, thus, are exquisitely equipped to be protected against oxidative stress consistent with their progenitor cell character...

..This highlights the crucial role of the p22phox-containing NAD(P)H oxidase in the ANG II and PDGF AA induced signal transduction pathway...

..Therefore, these results indicate that ROS generated by a gp91-independent NADPH oxidase(s) are important for establishing an adequate inflammatory response to pneumococcal CSF infection...

..We suggest that AT1-AA through activation of NADPH oxidase could contribute to ROS production and inflammatory responses in preeclampsia...

..Increased vasodilating responsiveness to endothelial NO contributes to compensate for the missing vasodilating effect of ANP in SMC GC-A KO mice...

..Cell-to-cell contact but not cellular fusion mediates EPC transdifferentiation. The therapeutic use of autologous EPCs may aid cardiomyocyte regeneration in patients with ischemic heart disease...

..These data identify a novel mechanism of autogeneration of endogenous PPAR-alpha ligands via stimulation of NADPH oxidase activity...

..Generated ROS interact with NO to produce peroxynitrite, which in turn activates MMPs, facilitating vessel remodeling. Our study provides the first evidence that ROS play a fundamental role in flow-induced vascular enlargement...

..Thus, our aims were to study the molecular and biochemical state of NADPH-oxidase in cirrhotic livers and to investigate its possible role in modulating hepatic vascular tone in cirrhosis...

..Here, we show that pharmacological enhancement of eNOS expression with AVE at least partially reverses the impaired functional activity of BMC from ICMP patients, highlighting the critical role of NO for progenitor cell function...

..Thus, inhibitory effects of this beta-blocker on vascular NADPH oxidase may explain, at least in part, its beneficial effect on endothelial function in angiotensin II-induced hypertension...

..Here, we investigated the role of p47phox in blood pressure control, endothelium-dependent relaxation, cardiac hypertrophy, RAS activation, and renal oxidative stress under resting conditions...

..In intrapulmonary arteries, endothelial dysfunction depends on gp91phox, the latter being rather the trigger than the mediator of impaired endothelial NO-dependent relaxation..

..Since NADPH oxidases are a major source of reactive oxygen species in the heart, we studied left ventricular remodeling after myocardial infarction in mice with targeted deletion of the NADPH oxidase subunit gp91(phox)...

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