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Biomedical subjects

E S Stroes

Publications and source records attributed to E S Stroes.

At least 19 recordsLinked to original sources
PubMed2006

Atherogenesis in rheumatology.

Atherosclerosis is a chronic inflammatory disorder characterized by immune cell activation, inflammation driven plaque formation and subsequent destabilization. In other disorders of an inflammatory nature, the chronic inflammatory state per se has been linked to acceleration of the atherosclerotic process which is underlined by an increased incidence of cardiovascular disease (CVD) in disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphopholipid (Hughes) syndrome (APS). In addition to systemic inflammation, additional mechanisms have been put forward that are more specific for the pathophysiology of the individual chronic inflammatory disorders.

Annexin A5↗
PubMed2001

Antioxidant capacity of mononitrosyl-iron-dithiocarbamate complexes: implications for NO trapping.

Using EPR spectroscopy, we show that the water-soluble mononitrosyl iron complexes with N-methyl-D-glucamine dithiocarbamate (MNIC-MGD) ligands can easily react with superoxide and with peroxynitrite. The reaction with superoxide transforms the paramagnetic MNIC-MGD complex into an EPR silent complex with a reaction rate of 3 x 10(7) (M.s)(-1). Suppletion of ascorbate partially restores the complexes to their original paramagnetic state. We propose that the reaction of MNIC-MGD with either superoxide or peroxynitrite leads to identical EPR silent complexes. Our results have important implications for the technique of NO trapping in biosystems with Fe-dithiocarbamate complexes, where mononitrosyl-iron complexes (hydrophilic as well as hydrophobic) are formed as adducts in the trapping reaction. This principle is illustrated by NO trapping experiments on viable cultured endothelial cells. We find that MNIC-MGD acts as a very potent and water-soluble antioxidant with an efficiency exceeding most SOD mimics. Moreover, by accounting for the EPR silent fraction of iron complexes, the sensitivity of NO trapping can be enhanced considerably. The method was demonstrated for hydrophobic iron-dithiocarbamate complexes in endothelial cell cultures, where sensitivity for NO detection was enhanced by a factor of 5.

Air↗
PubMed2001

Effect of statin versus fibrate on postprandial endothelial dysfunction: role of remnant-like particles.

BACKGROUND: Postprandial lipemia is associated with endothelial dysfunction. Remnant-like particles (RLP) have been suggested to contribute to these adverse vascular effects. We investigated the effect of cerivastatin and gemfibrozil upon oral fat load induced changes in endothelial function and postprandial lipid profile in vivo. METHODS: In a randomized cross-over trial, 15 healthy volunteers received cerivastatin (0.4 mg once daily), gemfibrozil (900 mg once daily) or placebo for 3 weeks. Lipid profiles and flow mediated dilation (FMD) were assessed before and 4 h after an oral fat load. Endothelium-independent dilation was tested after nitroglycerine 0.4 mg sublingual spray. RESULTS: After the placebo period, the oral fat load induced an increase in triglycerides (TG) and RLP-cholesterol (RLP-C) (0.9 +/- 0.7 and 0.08 +/- 0.04 mmol/l, respectively) and a significant decrease in FMD (9.1 +/- 3.4 to 4.3 +/- 3.3%, P < 0.05). After gemfibrozil, TG increase was attenuated (0.5 +/- 0.5 mmol/l), whereas RLP-C increase (0.05 +/- 0.09 mmol/l) and FMD decrease (9.0 +/- 3.8 to 5.2 +/- 2.6%, P < 0.05) were not different from placebo therapy. Cerivastatin did not affect TG increase (0.7 +/- 0.8 mmol/l). RLP-C increase (0.02 +/- 0.07 mmol/l) and FMD (7.9 +/- 2.6 to 8.4 +/- 2.8%) change were attenuated significantly compared to placebo. Endothelium-independent vasodilatation remained unaltered throughout the protocol. CONCLUSION: Cerivastatin, but not gemfibrozil significantly reduces RLP-C increase after an oral fat load in combination with a reversal of fat-load induced endothelial dysfunction. The present data imply that lowering of RLP-C, rather than lowering of total TG levels, may contributes to the prevention of endothelial dysfunction after an oral fat load during statin use.

Adolescent↗
PubMed2001

Variability of flow mediated dilation: consequences for clinical application.

BACKGROUND: Flow mediated vasodilatation (FMD), a non-invasive tool to assess endothelial function, has been shown to have prognostic value for the development of cardiovascular disease. Conventional B-mode ultrasonography has been criticised for its 'limited' resolution in vivo, which complicates reliable detection of the minute diameter changes during reactive hyperaemia. In the present study we evaluated the physical resolution, reproducibility and the capability to detect FMD impairment of a wall tracking system (WTS). METHODS: The resolution of WTS was compared with that of intravascular ultrasound (IVUS) in pig femoral arteries in vivo. Subsequently, intra- and interobserver variability of FMD testing with WTS was evaluated in 75 healthy volunteers. Finally, the effect of smoking as single risk factor for atherosclerosis on FMD in vivo was assessed. RESULTS: WTS and IVUS readings were not different (difference in arterial cross sectional area 1.97 mm(2), r=0.87). Intrasession coefficient of variation in baseline diameter was 1.1% (extremes 0.06--2.0%). Inter-session baseline diameter variation was 3.6 and 3.8% for each observer and 4.1% between observers. Intra-individual variability in FMD between sessions was considerable with coefficients of variation of 13.9% for FMD and 9.3% for NTG. Smokers had impaired FMD responses compared with matched non-smokers (4.7+/-2.4 vs. 9.6+/-4.4%, P<0.001), whereas NTG induced vasodilatation did not differ (13.4+/-6.2 vs. 15.4+/-5.1%; p=ns). CONCLUSION: WTS is a suitable technique for reproducibly assessing the brachial artery diameter in vivo with a accuracy comparable to that of IVUS. Using this sensitive technique the reproducibility of FMD in vivo proves to be poor mainly due to physiological factors. Whereas this seriously limits the use of FMD as follow-up parameter for individual subjects, FMD is demonstrated to be a useful research tool at group level.

Adult↗
PubMed2001

Placental superoxide is increased in pre-eclampsia.

One of the current hypotheses on the pathophysiology of pre-eclampsia (PE) states that the placenta secretes one or more cytotoxic factors resulting in maternal endothelial dysfunction. Among the candidate factors are the products of increased oxidative stress. Although there is circumstantial evidence of such an increase, direct evidence is still lacking. Electron paramagnetic spin trap resonance (EPR), the most direct method to detect free radicals in tissues, was used to measure superoxide levels in placentae from normal pregnancies (n=13) and pregnancies complicated by PE (n=10). The superoxide level was significantly increased in the placental tissue of pre-eclamptic women. Moreover, upon inhibition of Cu-Zn superoxide dismutase (SOD) activity the relative increase of the superoxide levels was significantly smaller in the placentae from the PE patients, implying decreased basal Cu-Zn SOD activity. These findings lend direct support to the hypothesis that oxidative stress in placental tissue is increased in PE.

Adult↗
PubMed2000

Folic acid reverts dysfunction of endothelial nitric oxide synthase.

5-methyltetrahydrofolate (MTHF), the active form of folic acid, has been reported to restore NO status in hypercholesterolemic patients. The mechanism of this effect remains to be established. We assessed the effects of L- and D-MTHF on tetrahydrobiopterin (BH(4))-free and partially BH(4)-repleted endothelial NO synthase (eNOS). Superoxide production of eNOS and the rate constants for trapping of superoxide by MTHF were determined with electron paramagnetic resonance using 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO) as spin trap for superoxide. NO production was measured with [(3)H]arginine-citrulline conversion or nitrite assay. The rate constants for scavenging of superoxide by L- and D-MTHF were similar, 1.4 x 10(4) ms(-1). In BH(4)-free eNOS, L- and D-MTHF have no effect on enzymatic activity. In contrast, in partially BH(4)-repleted eNOS, we observe a 2-fold effect of MTHF on the enzymatic activity. First, superoxide production is reduced. Second, NO production is enhanced. In cultured endothelial cells, a similar enhancement of NO production is induced by MTHF. In the present study, we show direct effects of MTHF on the enzymatic activity of NO synthase both in recombinant eNOS as well as in cultured endothelial cells, which provides a plausible explanation for the previously reported positive effects of MTHF on NO status in vivo.

Cells, Cultured↗
PubMed2000

Influence of folic acid on postprandial endothelial dysfunction.

Triglyceride-rich lipoproteins that circulate postprandially are increasingly being recognized as potentially atherogenic. These particles also have been shown to cause endothelial dysfunction. We recently demonstrated that acute parenteral administration of folic acid restores endothelial function in vivo in patients with increased LDL cholesterol levels. In vitro data suggested that this effect could be mediated by a reduction of radical stress. In the present study, therefore, we evaluated the effect of an acute oral fat load on both endothelial function and oxygen radical production. Next, we studied whether 2 weeks of pretreatment with 10 mg folic acid PO could prevent these fat-induced changes. We conducted a prospective, randomized, placebo-controlled study to evaluate the effect of oral folic acid administration (10 mg/d for 2 weeks) on basal endothelial function as well as endothelial function on an acute fat load in 20 healthy volunteers 18 to 33 years old. Endothelial function was assessed as flow-mediated dilatation (FMD). Endothelium-independent dilatation was measured after sublingual nitroglycerin spray. Oxygen radical stress was assessed by measurement of the urinary excretion of the stable radical-damage end product malondialdehyde. During administration of placebo, FMD decreased significantly after an acute oral fat load, with a median from 10.6% (8.3% to 12.2%) to 5.8% (3.0% to 10.2%), P<0.05. During folic acid administration, FMD was unaffected by a fat load, with a median from 9.6% (7.1% to 12.8%) to 9.9% (7.5% to 14.1%), P=NS. The increase in malondialdehyde excretion in the urine after fat loading was also prevented during folic acid administration (absolute increase after an acute fat load during placebo, 0.11+/-0.1 micromol/L versus folic acid, 0.02+/-0.1 micromol/L, P<0.05). The response to the endothelium-independent vasodilator nitroglycerin remained unaltered throughout the study. Pretreatment with oral folic acid prevents the lipid-induced decrease in FMD as well as the lipid-induced increase in urinary radical-damage end products. Because these observations were made in healthy volunteers with normal folate and homocysteine levels, it is suggested that a higher folate intake in the general population may have vasculoprotective effects.

Adolescent↗
PubMed1999

Effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor antagonism on postprandial endothelial function.

OBJECTIVES: The purpose of this study was to determine whether endothelial dysfunction as a consequence of direct postprandial lipid response might be favorably influenced by angiotensin-converting enzyme inhibitors or angiotensin AT1 receptor antagonists. BACKGROUND: Postprandial triglyceride-rich lipoproteins cause endothelial dysfunction. Angiotensin-converting enzyme inhibitors have been shown to improve vascular reactivity. For angiotensin II type 1 receptor antagonists this effect is as yet uncertain. METHODS: A randomized, double-blind, placebo-controlled crossover study in 30 healthy volunteers, aged 18 to 33 years, evaluated the effect of quinapril (40 mg daily for two weeks) and losartan (50 mg daily for two weeks) on basal as well as postprandial endothelial function measured noninvasively as percentage diameter change in the brachial artery after reactive hyperemia. Endothelium-independent dilation was measured after nitroglycerine spray sublingual. RESULTS: An acute oral fat load impaired endothelial function. Flow-mediated vasodilation (FMD) decreased from a median of 6.2% to 4.2% (p < 0.05). There was no significant difference in preprandial endothelial function after two weeks of treatment with either quinapril or losartan compared with placebo in these healthy volunteers. Both quinapril (FMD 6.4% to 6.3%) and losartan (7.1% to 5.4%) prevented endothelial dysfunction induced by an oral fat load, although the protective effect of quinapril appeared to be more profound. The response to the endothelium-independent vasodilator nitroglycerine was unaltered throughout the study. CONCLUSIONS: Both losartan and quinapril prevent endothelial dysfunction induced by triglyceride-rich lipoproteins in healthy volunteers. However, the protective effect of quinapril is more pronounced.

Adult↗
PubMed1999

Hypoalbuminemia increases lysophosphatidylcholine in low-density lipoprotein of normocholesterolemic subjects.

BACKGROUND: A phospholipid, lysophosphatidylcholine (LPC), is the major determinant of the atherosclerotic properties of oxidized low-density lipoprotein (LDL). Under normal circumstances most LPC is bound to albumin. We hypothesized that lipoprotein LPC concentrations are increased in hypoalbuminemic patients with the nephrotic syndrome, irrespective of their lipid levels. To test this hypothesis, we selected nephrotic and control subjects with matched LDL cholesterol levels. METHODS: Lipoproteins and the albumin-rich lipoprotein-deficient fractions were separated by ultracentrifugation and their phospholipid composition was analyzed by thin-layer chromatography. RESULTS: Nephrotic subjects (albumin 23 +/- 2 g/liter and LDL cholesterol 3.1 +/- 0.2 mmol/liter) had a LDL LPC concentration that was increased (P < 0.05) to 66 +/- 7 vs. 35 +/- 6 micromol/liter in matched controls (albumin 42 +/- 5 g/liter and LDL cholesterol 3.1 +/- 0.2 mmol/liter). LPC in very low-density lipoprotein plus intermediate-density lipoprotein (VLDL + IDL) in these subjects was also increased to 33 +/- 7 vs. 9 +/- 2 micromol/liter in controls (P < 0.05). Conversely, LPC was decreased to 19 +/- 4 micromol/liter in the albumin-containing fraction of these hypoalbuminemic patients, as compared to 46 +/- 10 micromol/liter in the controls (P < 0.05). LPC was also low (14 +/- 4 micromol/liter) in the albumin-containing fraction of hypoalbuminemic, hypocholesterolemic patients with nonrenal diseases. In hyperlipidemic nephrotic subjects (albumin 21 +/- 2 g/liter and LDL cholesterol 5.7 +/- 0.5 mmol/liter) the LPC levels in LDL and VLDL + IDL were further increased, to 95 +/- 20 and 56 +/- 23 micromol/liter, respectively (P < 0.05). CONCLUSION: These findings suggest that in the presence of hypoalbuminemia in combination with proteinuria, LPC shifts from albumin to VLDL, IDL and LDL. This effect is independent of hyperlipidemia. Increased LPC in lipoproteins may be an important factor in the disproportionate increase in cardiovascular disease in nephrotic patients with hypoalbuminemia.

Adolescent↗
PubMed1999

Endothelial function in proteinuric renal disease.

Nephrotic-range proteinuria is associated with a several-fold increase risk of cardiovascular infarction. This increased risk is accompanied by endothelial dysfunction, which is not related to increased blood pressure and is not correctable by acute administration of L-arginine. The latter is in direct contrast to what has been found in patients with primary hypercholesterolemia, suggesting that either hypoalbuminemia itself or other aspects of the dyslipidemia characteristic of the nephrotic syndrome impair endothelial function. Lysophosphatidylcholine (lyso-PC) is formed during oxidative modification of cholesterol, and lyso-PC in oxidized low-density lipoprotein (LDL) is responsible for reduced endothelial function in vitro. However, in the circulation, lyso-PC is tightly bound to albumin. Indeed, the addition of albumin can restore endothelial function, which was previously disturbed by lyso-PC. Hypoalbuminemia induces a shift in lyso-PC to lipoproteins, notably LDL, and to erythrocytes. The latter directly induces a reduction in deformability that can also be corrected by the addition of albumin. Hypoalbuminemia may disturb endothelial function, either by directly affecting Gi-protein-dependent signal transduction or indirectly by changing the configuration of the cell membrane. Such a change in cell membrane configuration will disturb binding of ligands to receptors and of endothelial nitric oxide (NO) synthase to caveolin. However, other pathways have been suggested, such as stimulation by lyso-PC of vasoconstriction mediated by protein kinase C. It remains to be shown whether lipid-lowering and antiproteinuric strategies have independent positive effects on endothelial function in nephrotic subjects.

Animals↗
PubMed1999

Acute simultaneous stimulation of nitric oxide and oxygen radicals by angiotensin II in humans in vivo.

Angiotensin II is a powerful vasoconstrictor and proatherogenic factor. It was recently suggested that the endothelium may influence the actions of angiotensin II by production of, for example, nitric oxide and superoxide. By using venous occlusion plethysmography, forearm blood flow was measured in 26 healthy subjects during intraarterial cumulative infusion of angiotensin II. In 14 subjects, the interaction between angiotensin II and NO was studied by infusion of angiotensin II before and after clamping NO availability at a fixed basal level by using N(G)-monomethyl-L-arginine (L-NMMA) and nitroprusside. During a "free" NO system, blood flow decreased on angiotensin II infusion from 2.70+/-0.30 ml/100 ml forearm/min to 1.38+/-0.15 ml/100 ml forearm/min, whereas during NO-clamp vasoconstriction was significantly enhanced (blood flow from 2.56+/-0.25 to 1.19+/-0.13; p<0.05 saline vs. NO clamp). In 12 other subjects, the interaction between angiotensin II and superoxide was evaluated by comparison of the effects of angiotensin II before and after coinfusion of vitamin C. Angiotensin II-induced vasoconstriction was significantly attenuated by vitamin C at higher dosages of angiotensin (saline, blood flow from 3.08+/-0.33 to 1.12+/-0.09; vitamin C, blood flow from 3.01+/-0.23 to 1.61+/-0.13; p<0.05 saline vs. vitamin C). Vitamin C had no effect on baseline forearm blood flow. In conclusion, this study demonstrates that the constrictor actions of angiotensin II are enhanced during NO clamp and attenuated during vitamin C, suggesting direct angiotensin II-associated stimulation of endothelial NO and of oxygen radicals, respectively, in humans in vivo.

Adult↗
PubMed1998

Nitric oxide availability in diabetes mellitus.

Diabetes mellitus is associated with early development of cardiovascular complications. Under physiological conditions the endothelium protects against the development of atherosclerosis. Endothelial cells produce, e.g., nitric oxide (NO), a substance which is capable of keeping vascular tone, coagulation and inflammation well balanced. However, in pathological conditions, such as in diabetes mellitus, impaired NO activity may be present. Decreased NO activity can be caused by impaired production of NO, due to uncoupling of receptor-mediated signal transduction, a deficiency of the NO synthase (NOS) substrate L-arginine, or a decreased availability of one or more cofactors essential for optimal functioning of NOS. However, hyperglycaemia also stimulates the production of advanced glycosylated end products, enhances the polyol pathway and activates protein kinase C. These conditions may lead to increased oxidative stress. Reactive oxygen species rapidly inactivate NO leading to the formation of peroxynitrite. Peroxynitrite is a toxic oxidant capable of damaging many biological molecules. Reduced NO availability may not only be of relevance to the development of atherosclerotic complications in diabetes but may also interfere with insulin-mediated postprandial glucose disposal and possibly contribute to the development of insulin resistance. Understanding of the complex metabolic disturbances interacting with the NO system may provide us with further therapeutic options to decrease cardiovascular morbidity and mortality in diabetes mellitus.

Animals↗
PubMed1998

Divergent effects of ACE-inhibition and calcium channel blockade on NO-activity in systemic and renal circulation in essential hypertension.

OBJECTIVE: Nitric oxide is a vasodilating and blood pressure lowering substance. To investigate whether calcium antagonists or angiotensin-converting enzyme (ACE) inhibitors increase vascular nitric oxide activity, we assessed systemic and renal vascular sensitivity to nitric oxide synthase inhibition in hypertensives on and off medication. METHODS: Ten essential hypertensive patients, aged 22-51 years, were studied 3 times: > or = 4 weeks off medication, after 3 weeks treatment with enalapril 20 mg twice a day and after 3 weeks nifedipine 60 mg/day. Each time, 24-h blood pressure registration was performed, followed by a clearance study to obtain a 3-h dose-response curve for intravenously infused NG-monomethyl-L-arginine (L-NMMA, respectively 0.75, 1.5 and 3.0 mg/kg/h). RESULTS: L-NMMA dose-dependently increased mean arterial pressure with 5 +/- 2 mmHg and systemic vascular resistance with 24 +/- 5% at maximum dose, whereas cardiac output decreased (all P < 0.001). Enalapril and nifedipine treatment decreased blood pressure, while the L-NMMA-induced increase in systemic vascular resistance was potentiated (enalapril: 45 +/- 7% and nifedipine: 46 +/- 8%; both P < 0.01). L-NMMA also dose-dependently decreased renal blood flow by 58 +/- 8% at maximum dose (P < 0.001), but neither drug potentiated these effects. CONCLUSION: These results indicate that, in essential hypertensives, antihypertensive therapy with enalapril or nifedipine increases nitric oxide dependency of systemic vascular tone, which may play a role in the blood pressure lowering effect of these drugs. However, this phenomenon cannot be observed in the renal circulation, suggesting a different regulation of endothelium-dependent vasomotion in the hypertensive kidney.

Adult↗
PubMed1998

Oxygen radical stress in vascular disease: the role of endothelial nitric oxide synthase.

Impaired nitric oxide (NO) activity in proatherosclerotic states has been suggested to be caused mainly by increased degradation of NO by oxygen radicals. In recent years, endothelial NO synthase has been identified as a system that contributes to oxygen radical stress under pathophysiologic conditions. We discuss the origin of NO synthase-derived superoxide production, as well as possibilities to modulate (pathologic) shifts in NO/superoxide production by endothelial NO synthase.

Animals↗
PubMed1997

Cyclosporin A increases nitric oxide activity in vivo.

The use of cyclosporine is complicated by its vaso-constrictive actions. In vitro cyclosporine has been associated with both decreased endothelium-dependent vasodilatation and increased nitric oxide activity. We studied the interaction between cyclosporine and endothelium-derived nitric oxide in seven healthy volunteers. Using venous-occlusion plethysmography, we measured forearm blood flow during intra-arterial infusion of serotonin, which in the concentrations used is a selective agonist of endothelial nitric oxide release, or NG-monomethyl-L-arginine, a specific inhibitor of nitric oxide synthase, during coinfusion of saline or cyclosporine (75 micrograms/min), respectively. During coinfusion of cyclosporine, forearm blood flow increased on maximal serotonin infusion from 2.9 (SE, 0.2) to 8.1 (0.9) mL/100 mL per minute in forearm tissue, which was significantly higher than the increase during saline coinfusion (3.0[0.3] to 6.0 [0.5]; P < .05). Cyclosporine infusion during a "free" nitric oxide system had no effect on basal forearm blood flow, but in significantly decreased forearm blood flow (21.7[2.8]%; P < .05) during fixed nitric oxide activity. These data suggest that acute administration of cyclosporine enhances both basal and receptor-stimulated nitric oxide activity. The mechanism is not clear but may include cyclosporine-induced shear stress as well as direct effects of cyclosporine. The latter was supported by our observation that gene expression of the enzyme nitric oxide synthase III was enhanced by approximately 50% after coincubation with cyclosporine. In conclusion, the present observation demonstrates that nitric oxide constitutes an important regulating mechanism that protects against cyclosporine-associated vasoconstriction in vivo.

Adult↗