321 research outputs found
Atherosclerosis and the two faces of endothelial nitric oxide synthase
No full text[No abstract available
17beta-Estradiol inhibits proliferation and migration of human vascular smooth muscle cells: similar effects in cells from postmenopausal females and in males
No full textOBJECTIVES: Cardiovascular disease is rare in premenopausal women, but increases after the menopause when hormone replacement therapy reduces coronary events. Vascular smooth muscle cell (SMC) proliferation and migration occur in atherosclerosis, restenosis and venous graft disease. We studied the effects of 17 beta-estradiol on SMC proliferation and migration. METHODS: SMC were cultured from saphenous veins of postmenopausal women and age-matched men. Cell growth was determined by 3H-thymidine incorporation and cell counting. Migration of SMC was assessed in 4-well chambers. SMC were seeded in one corner and PDGF-BB in filter paper glued onto the opposite wall. RESULTS: PDGF-BB (5 ng/ml for 24 h) similarly stimulated 3H-thymidine incorporation in female (511 +/- 57%; n = 8) and male (528 +/- 62%; n = 12) SMC. This was reduced by 17 beta-estradiol (10(-8)-10(-6) M; female 313 +/- 52%; male 337 +/- 54%; P < 0.05). PDGF-BB increased the number of SMC (P < 0.0001 at 10 days) obtained from females (153 +/- 3%; n = 5) and males (150 +/- 4%; n = 5), which was inhibited by 17 beta-estradiol (10(-6) M; female 134 +/- 7%; male 128 +/- 5%; P < 0.05). Similar results were obtained with basic fibroblast growth factor. In contrast to 17 beta-estradiol, another steroid (dexamethasone) had no effects on 3H-thymidine incorporation in these cells stimulated with PDGF-BB, PDGF-BB (0.01-1 ng) stimulated SMC migration (P < 0.05) which was inhibited by 17 beta-estradiol (10(-10)-10(-6) M; n = 5; P < 0.005). CONCLUSION: 17 beta-Estradiol inhibits growth-factor-induced SMC proliferation and migration regardless of gender. These effects of 17 beta-estradiol may contribute to its cardiovascular protective properties in postmenopausal women during replacement therap
Tetrahydrobiopterin restores endothelial function in hypercholesterolemia
No full textIn hypercholesterolemia, impaired nitric oxide activity has been associated with increased nitric oxide degradation by oxygen radicals. Deficiency of tetrahydrobiopterin, an essential cofactor of nitric oxide synthase, causes both impaired nitric oxide activity and increased oxygen radical formation. In this study we tested whether tetrahydrobiopterin deficiency contributes to the decreased nitric oxide activity observed in hypercholesterolemic patients. Therefore, L-mono-methyl-arginine to inhibit basal nitric oxide activity, serotonin to stimulate nitric oxide activity, and nitroprusside as endothelium-independent vasodilator were infused in the brachial artery of 13 patients with familial hypercholesterolemia and 13 matched controls. The infusions were repeated during coinfusion of L-arginine (200 mu g/kg/min), tetrahydrobiopterin (500 mu g/min), or the combination of both compounds. Forearm vasomotion was assessed using forearm venous occlusion plethysmography and expressed as ratio of blood flow between measurement and control arm (M/C ratio). Tetrahydrobiopterin infusion alone did not alter M/C ratio. Both the attenuated L-mono-methyl-arginine-induced vasoconstriction as well as the impaired serotonin-induced vasodilation were restored in patients during tetrahydrobiopterin infusion. Tetrahydrobiopterin had no effect in controls. In conclusion, this study demonstrates restoration of endothelial dysfunction by tetrahydrobiopterin suppletion in hypercholesterolemic patients
Endothelin blockers and renal protection: a new strategy to prevent end-organ damage in cardiovascular disease?
No full textIslet transplantation in type 1 diabetes
No full textHanneke de Kort, research fellow1, Eelco J de Koning, associate professor, head of clinical islet transplantation programme234, Ton J Rabelink, professor of medicine, chair of department of nephrology2, Jan A Bruijn, professor immunopathology1, Ingeborg M Bajema, renal and transplantation pathologist11Department of Pathology, Leiden University Medical Centre, 2300 RC Leiden, Netherlands2Department of Nephrology, Leiden University Medical Centre3Department of Endocrinology, Leiden University Medical Centre4Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, NetherlandsCorrespondence to: E J P de Koning e.dekoning{at}lumc.nlAccepted 10 December 2010Summary pointsIslet of Langerhans transplantation is used in a select group of patients with type 1 diabetes with severe glycaemic lability, recurrent hypoglycaemia, and hypoglycaemia unawarenessThe procedure is minimally invasive, with few procedure related complicationsTwo to three islet infusions are usually needed to achieve insulin independenceMost patients need insulin by five years post-transplantation owing to declining graft function; beneficial effects on the frequency of hypoglycaemic episodes and hypoglycaemia awareness remainMost long term complications are related to systemic immunosuppressionThe risk-benefit ratio of islet transplantation should be carefully weighed by the treating physician and the potential recipient, who should be given adequate informationA clinical review in the BMJ in 2001 anticipated that by 2010 transplantation of islets of Langerhans would be the treatment of choice for most patients with type 1 diabetes.1 Currently, islet transplantation is an option for a specific group of patients with type 1 diabetes only—those with severe glycaemic lability, recurrent hypoglycaemia, and hypoglycaemia unawareness. Patients with type 1 diabetes—who must deal with daily subcutaneous insulin injections, regular finger pricks for glucose measurements, and worries about hypoglycaemic episodes and long term complications of diabetes, hope for a cure for their disease and may ask their doctors about islet transplantation. Therefore, doctors who treat such patients should understand the potential benefits of islet transplantation as well as the hurdles that need to be overcome before it is widely used (box 1).Sources and selection criteriaWe searched PubMed, Embase, Web of Science, Cochrane, CINAHL, Academic Search Premier, and ScienceDirect using the keyword “islet transplantation”. We limited our search to the English language and to human studies. We found no randomised controlled trials, and most publications lacked an appropriate control group that was intensively managed by insulin using modern treatment regimens. Data were mainly derived from case series, follow-up
Meeting report: ISN forefronts in nephrology on endothelial biology and renal disease: from bench to prevention
No full textThis ISN-sponsored Forefront in Nephrology meeting, which has brought together 120 scientists from 21 countries, has been concerned with various aspects of endothelial function and dysfunction and their contribution to progression of chronic kidney disease and/or its cardiovascular complications. The following themes were discussed in great depth: (1) phenotypical changes in the vascular endothelium – permeability, senescence, and apoptosis; (2) regulation of endothelial nitric oxide (NO) synthase function – caveolar and shear stress mechanisms, epigenetic regulation, S-nitrosylation, and Rho-kinase regulation; (3) oxidative stress and hypoxia-induced changes; (4) organellar dysfunction – lysosomes, mitochondria, and endoplasmic reticulum; (5) NO-independent mechanisms of vasomotion – epoxides, heme oxygenase-1 and carbon monoxide, thromboxane, tumor necrosis factor-alpha, and uric acid; (6) endothelial crosstalk with podocytes, monocytes, smooth muscle cells, and platelets; (7) candidate clinical biomarkers of endothelial dysfunction – functional testing of macro- and micro-vascular functions, surrogate markers, circulating detached endothelial cells, and endothelial precursor cells; and culminated in Round Table discussion on the diagnosis of endothelial dysfunction and its treatment options. In conclusion, this meeting has focused on several key problems of endothelial cell pathobiology relevant to chronic kidney disease
A logistic regression model for microalbuminuria prediction in overweight male population
No full textBackground: Obesity promotes progression to microalbuminuria and increases the risk of chronic kidney disease. Current protocols of screening microalbuminuria are not recommended for the overweight or obese.

Design and Methods: A cross-sectional study was conducted. The relationship between metabolic risk factors and microalbuminuria was investigated. A regression model based on metabolic risk factors was developed and evaluated for predicting microalbuminuria in the overweight or obese.

Results: The prevalence of MA reached up to 17.6% in Chinese overweight men. Obesity, hypertension, hyperglycemia and hyperuricemia were the important risk factors for microalbuminuria in the overweight. The area under ROC curves of the regression model based on the risk factors was 0.82 in predicting microalbuminuria, meanwhile, a decision threshold of 0.2 was found for predicting microalbuminuria with a sensitivity of 67.4% and specificity of 79.0%, and a global predictive value of 75.7%. A decision threshold of 0.1 was chosen for screening microalbuminuria with a sensitivity of 90.0% and specificity of 56.5%, and a global predictive value of 61.7%.

Conclusions: The prediction model was an effective tool for screening microalbuminuria by using routine data among overweight populations
Cellular regulation of endothelial nitric oxide synthase.
No full textInternational audienceRenal function is highly dependent on endothelium-derived nitric oxide (NO). Several renal disorders have been linked to impaired NO bioavailability. The enzyme that is responsible for the synthesis of NO within the renal endothelium is endothelial NO synthase (eNOS). eNOS-mediated NO generation is a highly regulated cellular event, which is induced by calcium-mobilizing agonists and fluid shear stress. eNOS activity is regulated at the transcriptional level but also by a variety of modifications, such as acylation and phosphorylation, by its cellular localization, and by protein-protein interactions. The present review focuses on the complex regulation of eNOS within the endothelial cell
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