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Hydrogen peroxide regulation of endothelial function: Origins, mechanisms, and consequences

Published on Oct 1, 2005in Cardiovascular Research7.01
· DOI :10.1016/j.cardiores.2005.06.021
Hua Cai43
Estimated H-index: 43
(U of C: University of Chicago)
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Abstract
Increased production of reactive oxygen species (ROS) has been implicated in the pathogenesis of cardiovascular diseases. Enzymatic systems such as the mitochondrial respiratory chain, vascular NAD(P)H oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase (eNOS) produce superoxide anion (O2.−) in vascular cells. While some O2.− rapidly degrades by reacting with nitric oxide (NO.), the O2.− signal preserved by dismutation into hydrogen peroxide (H2O2) exerts prolonged signaling effects. This review focuses on patterns and mechanisms whereby H2O2 modulates different aspects of endothelial cell function including endothelial cell growth and proliferation, endothelial apoptosis, endothelium-dependent vasorelaxation, endothelial cytoskeletal reorganization and barrier dysfunction, endothelial inflammatory responses, and endothelium-regulated vascular remodeling. These modulations of endothelial cell function may at least partially underlie H2O2 contribution to the development of vascular disease.
  • References (141)
  • Citations (411)
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References141
Newest
Karel Chalupsky6
Estimated H-index: 6
,
Hua Cai43
Estimated H-index: 43
Recent studies demonstrate that oxidative inactivation of tetrahydrobiopterin (H4B) may cause uncoupling of endothelial nitric oxide synthase (eNOS) to produce superoxide (). H4B was found recyclable from its oxidized form by dihydrofolate reductase (DHFR) in several cell types. Functionality of the endothelial DHFR, however, remains completely unknown. Here we present findings that specific inhibition of endothelial DHFR by RNA interference markedly reduced endothelial H4B and nitric oxide (NO·...
Radia Forteza7
Estimated H-index: 7
,
Matthias A Salathe36
Estimated H-index: 36
+ 2 AuthorsGregory E. Conner33
Estimated H-index: 33
Hydrogen peroxide (H(2)O(2)) is found in exhaled breath and is produced by airway epithelia. In addition, H(2)O(2) is a necessary substrate for the airway lactoperoxidase (LPO) anti-infection system. To investigate the source of H(2)O(2) produced by airway epithelia, PCR was used to screen nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression in human airway epithelia redifferentiated at the air-liquid interface (ALI) and demonstrated the presence of Duox1 and 2. Western blots o...
Published on Mar 17, 2005in Circulation Research15.86
Hua Cai43
Estimated H-index: 43
(U of C: University of Chicago)
Excessive production of reactive oxygen species in the vasculature contributes to cardiovascular pathogenesis. Among biologically relevant and abundant reactive oxygen species, superoxide (O 2 ·− ) and hydrogen peroxide (H 2 O 2 ) appear most important in redox signaling. Whereas O 2 ·− predominantly induces endothelial dysfunction by rapidly inactivating nitric oxide (NO · ), H 2 O 2 influences different aspects of endothelial cell function via complex mechanisms. This review discusses recent a...
Published on Mar 1, 2005in Antioxidants & Redox Signaling5.83
Buul van J. D5
Estimated H-index: 5
,
Mar Fernandez-Borja24
Estimated H-index: 24
+ 1 AuthorsPeter L. Hordijk49
Estimated H-index: 49
Reactive oxygen species (ROS) control the integrity of the vascular endothelium. Our laboratory has recently shown that transduction of human umbilical vein endothelial cells (HUVECs) with an active variant of the small GTPase Rac promotes the production of ROS, ROS-dependent activation of p38 mitogen-activated protein kinase, and loss of vascular/endothelial-cadherin-mediated cell–cell adhesion. Here we show that HUVECs express mRNAs for NOX2 as well as NOX4 mRNA, but not for NOX1 or NOX3. Inte...
Published on Mar 1, 2005in Free Radical Biology and Medicine5.66
Talija Djordjevic14
Estimated H-index: 14
(TUM: Technische Universität München),
Alexej Pogrebniak2
Estimated H-index: 2
(TUM: Technische Universität München)
+ 5 AuthorsAgnes Görlach47
Estimated H-index: 47
(TUM: Technische Universität München)
Endothelial dysfunction is characterized by increased levels of reactive oxygen species (ROS) and a prothrombotic state. The mechanisms linking thrombosis to ROS production in the endothelium are not well understood. We investigated the role of thrombin in regulating NADPH oxidase-dependent ROS production and expression of its subunit p22phox in the endothelial cell line EaHy926. Thrombin elicited a biphasic increase in ROS generation peaking within 15 min, but also at 3 h. The delayed response ...
David S. Weber15
Estimated H-index: 15
(Emory University),
Petra Rocic5
Estimated H-index: 5
(Emory University)
+ 4 AuthorsKathy K. Griendling92
Estimated H-index: 92
(Emory University)
Increased reactive oxygen species (ROS) are implicated in several vascular pathologies associated with vascular smooth muscle hypertrophy. In the current studies, we utilized transgenic (Tg) mice (Tg p22smc ) that overexpress the p22 phox subunit of NAD(P)H oxidase selectively in smooth muscle. These mice have a twofold increase in aortic p22 phox expression and H2O2 production and thus provide an excellent in vivo model in which to assess the effects of increased ROS generation on vascular smoo...
Karine Laude9
Estimated H-index: 9
(Emory University),
Hua Cai43
Estimated H-index: 43
(U of C: University of Chicago)
+ 11 AuthorsSergey Dikalov57
Estimated H-index: 57
(Emory University)
Protein levels and polymorphisms of p22 phox have been suggested to modulate vascular NAD(P)H oxidase activity and vascular production of reactive oxygen species (ROS). We sought to determine whether increasing p22 phox expression would alter vascular ROS production and hemodynamics by targeting p22 phox expression to smooth muscle in transgenic (Tg) mice. Aortas of Tg p22smc mice had increased p22 phox and Nox1 protein levels and produced more superoxide and H2O2. Surprisingly, endothelium-depe...
Published on Jan 1, 2005in Cardiovascular Research7.01
Ralf P. Brandes69
Estimated H-index: 69
(Heidelberg University),
Jörg Kreuzer26
Estimated H-index: 26
Oxygen-derived free radicals are thought to contribute to the initiation and progression of cardiovascular disease via several different mechanisms, such as consumption of nitric oxide, oxidation of proteins and lipids, and activation of redox-sensitive signalling cascades. Vascular NADPH oxidases are important sources of vascular radical formation. The activities of these enzymes, which in some aspects are similar to the leukocyte NADPH oxidase, are controlled on the expression level and comple...
Published on Dec 2, 2004in Circulation Research15.86
Robert Fürst19
Estimated H-index: 19
,
Corinna Brueckl2
Estimated H-index: 2
+ 5 AuthorsAlexandra K. Kiemer32
Estimated H-index: 32
The cardiovascular hormone atrial natriuretic peptide (ANP) exerts anti-inflammatory effects on tumor necrosis factor-α–activated endothelial cells by inducing mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1). The underlying mechanisms are as yet unknown. We aimed to elucidate the signaling pathways leading to an induction of MKP-1 by ANP in primary human endothelial cells. By using antioxidants, generation of reactive oxygen species (ROS) was shown to be crucially involved in MKP-1...
Published on Nov 29, 2004in Arteriosclerosis, Thrombosis, and Vascular Biology6.62
Alec Weisberg3
Estimated H-index: 3
,
Francisco Albornoz2
Estimated H-index: 2
+ 5 AuthorsNancy J. Brown62
Estimated H-index: 62
Objective— To test the hypothesis that pharmacological plasminogen activator inhibitor (PAI)-1 inhibition protects against renin-angiotensin-aldosterone system-induced cardiovascular injury, the effect of a novel orally active small-molecule PAI-1 inhibitor, PAI-039, was examined in a mouse model of angiotensin (Ang) II-induced vascular remodeling and cardiac fibrosis. Methods and Results— Uninephrectomized male C57BL/6J mice were randomized to vehicle subcutaneus, Ang II (1 μg/h) subcutaneous, ...
Cited By411
Newest
Published on Jan 1, 2020in Redox biology7.79
Aleksandra Kopacz1
Estimated H-index: 1
(Jagiellonian University),
Damian Kloska2
Estimated H-index: 2
(Jagiellonian University)
+ 9 AuthorsJozef Dulak44
Estimated H-index: 44
(Jagiellonian University)
Abstract Premature senescence, a death escaping pathway for cells experiencing stress, is conducive to aging and cardiovascular diseases. The molecular switch between senescent and apoptotic fate remains, however, poorly recognized. Nrf2 is an important transcription factor orchestrating adaptive response to cellular stress. Here, we show that both human primary endothelial cells (ECs) and murine aortas lacking Nrf2 signaling are senescent but unexpectedly do not encounter damaging oxidative str...
Published on Sep 11, 2019in bioRxiv
Shin Yoo7
Estimated H-index: 7
(NU: Northwestern University),
Anna Pfenniger (NU: Northwestern University)+ 13 AuthorsSuzanne Bull (NU: Northwestern University)
Atrial fibrillation is the most common heart rhythm disorder in adults and a major cause of stroke. Unfortunately, current treatments of AF are suboptimal as they are not targeted to the molecular mechanisms underlying AF. In this study, we demonstrated using a novel gene-based strategy in a clinically relevant large animal of AF that oxidative injury is a key mechanism underlying the onset and perpetuation of AF. First, we demonstrated that generation of oxidative injury in atrial myocytes is a...
Published on Jun 1, 2019in Journal of Hepatology18.95
H.R. Wilman1
Estimated H-index: 1
(University of Westminster),
Constantinos Parisinos2
Estimated H-index: 2
(UCL: University College London)
+ 11 AuthorsHarry Hemingway56
Estimated H-index: 56
(UCL: University College London)
Abstract Background & Aims Excess liver iron content is common and is linked to hepatic and extrahepatic disease risk. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods First, we performed a genome-wide association study (GWAS) in 8,289 individuals in UK Biobank with MRI quantified liver iron, and validated our findings in an independent cohort (n=1,513 from IMI DIRECT). Second, we used Mendelian ran...
Published on Jan 1, 2019in Frontiers in Cardiovascular Medicine
Michael Kitching4
Estimated H-index: 4
(DCU: Dublin City University),
Denise Burtenshaw3
Estimated H-index: 3
(DCU: Dublin City University)
+ 1 AuthorsPaul A. Cahill36
Estimated H-index: 36
(DCU: Dublin City University)
Arteriosclerosis causes significant morbidity and mortality worldwide. Central to this process is the development of subclinical non-atherosclerotic intimal lesions before the appearance of pathologic intimal thickening and advanced atherosclerotic plaques. Intimal thickening is associated with several risk factors, including oxidative stress due to reactive oxygen species (ROS), inflammatory cytokines and lipid peroxidation. The main ROS producing systems in-vivo are reduced nicotinamide dinucl...
Cesar A. Meza , Justin D. La Favor7
Estimated H-index: 7
+ 1 AuthorsRobert C. Hickner34
Estimated H-index: 34
NADPH oxidases (NOX) are enzyme complexes that have received much attention as key molecules in the development of vascular dysfunction. NOX have the primary function of generating reactive oxygen species (ROS), and are considered the main source of ROS production in endothelial cells. The endothelium is a thin monolayer that lines the inner surface of blood vessels, acting as a secretory organ to maintain homeostasis of blood flow. The enzymatic production of nitric oxide (NO) by endothelial NO...
Wattanased Jarisarapurin (SWU: Srinakharinwirot University), Wariya Sanrattana (MU: Mahidol University)+ 2 AuthorsSuvara K. Wattanapitayakul9
Estimated H-index: 9
(SWU: Srinakharinwirot University)
It has been proven that high consumption of fruit and vegetable lowers the risks of cardiovascular and other oxidative stress-related diseases. Here we evaluated the effects of a tropical fruit, unripe Carica papaya (UCP), on endothelial protection against oxidative damage induced by H2O2. The antioxidant properties of UCP were investigated using the assays of FRAP and ORAC and specific ROS scavenging activities (H2O2, , OH•, HOCl). Cytoprotective property was tested in human endothelial cell li...
Published on May 1, 2019in Biochimica et Biophysica Acta3.79
David R. Zhou1
Estimated H-index: 1
(McGill University),
Rawan Eid6
Estimated H-index: 6
(McGill University)
+ 3 AuthorsMichael T. Greenwood21
Estimated H-index: 21
(RMC: Royal Military College of Canada)
Abstract Alterations in the levels of numerous second messengers are ubiquitous responses to all stresses that lead to apoptotic or hormetic responses. The sheer number and vast diversity of different second messenger systems activated in response to stresses belies a complexity that is often overlooked. This negligence is in large part due to the excessive focus on classical stress responsive second messenger mediators of stress especially Reactive Oxygen Species (ROS) but also others like calc...
Published on Apr 1, 2019in Biochemical and Biophysical Research Communications2.71
Kun Hu (Yangtze University), Qian Wan
Abstract HMG-CoA reductase inhibitor statins are used to treat patients with hypercholesterolemia. The pleiotropic effects of statins have been recently extended to the regulation of angiogenesis. However, the observations on the effects of statins on endothelial cells seem to be contradictory. In this work, we systematically analysed the effects of pravastatin at concentrations covering 10,000-fold range on the functions of human cardiac microvascular endothelial cells (HMVEC-C) under H 2 O 2 -...
Published on Feb 6, 2019in Oxidative Medicine and Cellular Longevity4.87
Cristiana Caliceti6
Estimated H-index: 6
(UNIBO: University of Bologna),
Anna Laura Capriotti27
Estimated H-index: 27
(Sapienza University of Rome)
+ 9 AuthorsMara Mirasoli26
Estimated H-index: 26
(UNIBO: University of Bologna)
The large amount of cauliflower industry waste represents an unexplored source of bioactive compounds. In this work, peptide hydrolysates from cauliflower leaves were characterized by combined bioanalytical approaches. Twelve peptide fractions were studied to evaluate unexplored biological activities by effect-based cellular bioassays. A potent inhibition of intracellular xanthine oxidase activity was observed in human vascular endothelial cells treated with one fraction, with an IC50 = . A diff...
Published on Jan 1, 2019
Joshua C. Tremblay7
Estimated H-index: 7
(UM: University of Michigan),
Joshua C. Tremblay1
Estimated H-index: 1
(UM: University of Michigan),
Kyra E. Pyke1
Estimated H-index: 1
(UM: University of Michigan)
The vascular endothelium is a single layer of cells that lines the luminal surface of blood vessels. Changes in blood flow alter the frictional force (shear stress) of the blood against endothelial cells resulting in biochemical signaling. Chronically, the magnitude and pattern of shear stress to which the endothelium is exposed play a key role in determining its function and structure. Regular exercise reduces cardiovascular disease risk, and the multifaceted mechanisms of this beneficial effec...
View next paperEndothelial Dysfunction in Cardiovascular Diseases: The Role of Oxidant Stress