Vascular renin-angiotensin-system, endothelial function and atherosclerosis?

Holtz, J.; Goetz, Regina

doi:10.1007/978-3-642-85660-0_7

Cited by 18 publications

(10 citation statements)

References 87 publications

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“…The described significant induction of gp91-phox expression at higher Ang II concentrations in the presence of a specific AT 2 receptor antagonist supports the view that repression of gp91-phox expression and O 2 Ϫ formation at high Ang II concentration is at least partially mediated by AT 2 receptor stimulation. Because a similar affinity to Ang II was shown for AT 1 and AT 2 receptors, 33 the different threshold levels of AT 1 receptormediated induction and AT 2 receptor-mediated repression of gp91-phox expression might result from differences in receptor density. Because cultured ECs express AT 1 receptors in excess compared with AT 2 receptors, 34 higher Ang II concentrations might be necessary for AT 2 receptor stimulation.…”

Section: Discussionmentioning

confidence: 87%

“…1,2 This hypothesis is supported by recent studies with Ang II receptor type 1 (AT 1 ) inhibitors, which show antiatherosclerotic effects in experimental studies 3 and reversal of endothelial dysfunction in patients with coronary artery disease. 4 Furthermore, ACE inhibitor therapy has a positive effect on the prognosis of patients with coronary artery disease.…”

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confidence: 95%

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Dose-Dependent Regulation of NAD(P)H Oxidase Expression by Angiotensin II in Human Endothelial Cells

Rueckschloss

Quinn

Holtz

et al. 2002

ATVB

192

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Objective-Angiotensin II (Ang II)-mediated induction of vascular superoxide anion formation could contribute to the development of endothelial dysfunction, hypertension, and atherosclerosis. An NAD(P)H oxidase has been identified as a major endothelial source of superoxide anions. However, the molecular mechanism underlying the regulation of NAD(P)H oxidase activity in response to Ang II is not well understood. Methods and Results-We investigated the dose-dependent regulation of superoxide anion formation and of NAD(P)H oxidase subunit expression in response to Ang II in human endothelial cells. Ang II regulates superoxide anion formation and the limiting subunit of endothelial NAD(P)H oxidase, gp91-phox, in a dose-dependent manner via Ang II type 1 (AT 1 ) receptor-mediated induction and Ang II type 2 receptor-mediated partial inhibition at higher Ang II concentrations. Furthermore, AT 1 receptor blocker therapy before coronary bypass surgery downregulates the gp91-phox expression in internal mammary artery biopsies of patients with coronary artery disease. Conclusions-Our

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Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 95%

Dose-Dependent Regulation of NAD(P)H Oxidase Expression by Angiotensin II in Human Endothelial Cells

Rueckschloss

Quinn

Holtz

et al. 2002

ATVB

192

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“…The inverse relationship between intracellular ACE and nitrite/nitrate levels observed by us in urate-treated HUVEC supports the proposed link between ACE and NOS activity. NO is a potent signaling molecule in endothelial cells modulating vascular tone, platelet activation, leukocyte adhesion to endothelium, and smooth muscle proliferation [28,29,30]. Earlier studies revealed…”

Section: Acknowledgmentsmentioning

confidence: 99%

Effect of Elevated Uric Acid Concentrations on Different Metabolic and Regulatory Parameters of Human Endothelial Cells (HUVEC) in Culture

Kühne¹,

Kopprasch²,

Gräßler³

et al. 1999

LaboratoriumsMedizin

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Endothelial injury and loss of normal endothelial function are key events for the development of coronary heart disease (CHD), hypertension, diabetes, and atherosclerosis. As a part of metabolic syndrome hyperuricemia often accompanies these diseases. The aim of this study was to investigate whether interaction of uric acid with endothelial cells (HUVEC) alters their structural and functional integrity. Therefore, the cell monolayers were incubated with medium containing increasing concentrations of uric acid (250, 500, 1000 / ) for various times (0, 24, 48, 72, 96 hours) at 37 °C and 5% CO 2 in a humidified incubator. To assess the degree of endothelial injury we measured the kinetics of release of various enzymes (angiotensin-converting enzyme, lactate dehydrogenase, N-acetyl-ß-D-glucosaminidase) from the cells and the amount of thiobarbituric acid reactive substances (TEARS). Additionally, the functional integrity of HUVEC was estimated by measuring urateinduced changes of intracellular regulatory metabolites as nitrate/nitrite and neopterin. In conclusion, our study has demonstrated considerable modifications of biochemical markers of endothelial cell membrane permeability after incubation with elevated concentrations of uric acid. The extent of endothelial injury correlated with the uric acid concentration and the duration of the incubation period. Intracellular NOS activity and neopterin levels were affected to a lesser extent suggesting that functional integrity of HUVEC was not impaired in the experimental conditions used.

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“…57 Angiotensin I1 may also have a pro-atherogenic effect mediated by the down-regulation of nitric oxide, which is antiatherogenic. 58 In a Pans study of 316 non-insulindependent diabetic patients, a group who commonly develop atherosclerosis and are therefore at increased risk of coronary heart disease (CHD), there was a higher prevalence of the DD genotype (0.43) in the 132 patients who had CHD than in the 184 patients who did not (0.29; OR of DDlII and IDIII 2.4 and 1.4, respe~tively).~~ The D D genotype appeared to be an independent risk factor and was the highest risk factor in males f o r C H D (relative risk 1.8 compared with 1.4 f o r smoking and 1.2 for elevated triglycerides). At least 24% of CHD was, moreover, attributed to the D allele, the true value being higher in view of the likely early mortality from its effects.…”

Section: Effect On Heartmentioning

confidence: 99%

Hypothesis: An Angiotensin Converting Enzyme/Genotype, Present in One in Three Caucasians, Is Associated With an Increased Mortality Rate

Morris

1996

Clin Exp Pharma Physio

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1. This review argues that the deletion (0) allele of an insertion (I)/deletion polymorphism of the angiotensin Iconverting enzyme (ACE) gene is a marker for a variant associated with increased ACE expression, as well as myocardial infarction (MI) and other lifethreatening conditions.2. By examination of I/D frequency in different age groups of individuals having well-known risk factors, it appears that homozygosity for the D allele may be associated with an increased risk of premature death in subjects at high-risk of cardiovascular events. For the risk factor hypertension, the odds ratio for DD vs II in patients aged 2 6 0 years was 6.6. 3. Besides in MI itself, the DD genotype appears to be also more prevalent in MI patients who develop restenosis several months after balloon angioplasty, patients with various forms of heart failure, those with ventricular hypertrophy and diabetic patients who develop nephropathy.4. Particular genotypes of other components of the reninangiotensin system may add to the risk conferred by the ACE DD genotype. 5.Emerging evidence therefore suggests that the ACE genotype may eventually be placed on the list of common, wellknown risk factors for fatal cardiovascular events. List of abbreviations: ACE Angiotensin converting enzyme ID Genotype heterozygous for the I/D polymorphism (k. AngIl Angiotensin I1 one allele of each) BMI Body mass index I1 Genotype heterozygous for the I allele 38. B$hn M. Berge KE. Bakken A, Erikssen J. Berg K. Insertion/ deletion ( / I D ) polymorphism at the locur for rngiotensin 1converting enzyme and parental history of myocardial infarction. clin. Genet. 1993; 44: 298-301. 39. Mitttinen H, Korpela K. HimlYIlIinen L. Kontula K. Polymorphisms of the apolipoprotein 8nd angiotcnsin Converting enzyme genei in young North Karelian patients with coronheart disease. Ilum. Genet. 1994.94 189-92. 4. Mattu RK. Needham EWA. Galton DJ. Frangos E, Clark A J k Caulfield M. A DNA variant at the nngiotensin-converting c n z m e Y gene locus associates with coronary artery disease in the Caerphill }{Cart Study. Circulurlon 1995; 91: 270-4. 41. Badenhop R E Wan8 XL. Wilcken DEL. Angiotensinconvcrting 1993; 8 5 189-95. 169-80.

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Vascular renin-angiotensin-system, endothelial function and atherosclerosis?

Cited by 18 publications

References 87 publications

Dose-Dependent Regulation of NAD(P)H Oxidase Expression by Angiotensin II in Human Endothelial Cells

Dose-Dependent Regulation of NAD(P)H Oxidase Expression by Angiotensin II in Human Endothelial Cells

Effect of Elevated Uric Acid Concentrations on Different Metabolic and Regulatory Parameters of Human Endothelial Cells (HUVEC) in Culture

Hypothesis: An Angiotensin Converting Enzyme/Genotype, Present in One in Three Caucasians, Is Associated With an Increased Mortality Rate

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