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Results for “Endothelial function”

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PubMed2005

Heart rate recovery after exercise and endothelial function--two important factors to predict cardiovascular events.

An attenuated heart rate recovery immediately after exercise, thought to be a marker of reduced parasympathetic activity, has been demonstrated to be an independent predictor of all-cause mortality in several large-scale studies; however, the mechanisms by which impaired heart rate recovery confers an increased risk of death are not clear. From clinical observation, vagal reactivation was thought to be the major determinant of the decrease in heart rate during the first 30 seconds of recovery, independent of age and the intensity of exercise; however, patients with attenuated heart rate recovery were also shown to have lower exercise workload, shorter exercise duration, lower numbers achieving 90% target heart rate, and even impaired endothelial function. This review focuses on the roles of heart rate recovery and endothelial function in predicting future mortality and their interaction.

Age Factors↗

PubMed2003

Preservation of endothelial function by the HMG-CoA reductase inhibitor fluvastatin through its lipid-lowering independent antioxidant properties in atherosclerotic rabbits.

Recent evidence suggests that the beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on entothelial function and cardiovascular ischemic events may be attributed not only to their lipid-lowering effects but also to cholesterol-lowering independent (direct) effects on the atherosclerotic vessel wall. This study was designed to test the hypothesis that fluvastatin (Flu) preserves the endothelial function by its cholesterol-lowering independent actions. Rabbits were fed a 0.5% high-cholesterol (HC) diet for 12 weeks (progression phase) and then fed the HC diet either containing or not containing Flu 2 mg/kg/day for an additional 8 weeks (treatment phase). Rabbits fed a normal diet were used as controls. Plasma total and low-density lipoprotein cholesterol concentrations did not differ during the treatment phase: Endothelium-dependent/NO-mediated relaxation (acetylcholine and A23187) was impaired in the HC diet group, whereas it was preserved in the HC plus Flu treatment group. The endothelium-independent relaxation (sodium nitroprusside) was similar between the three groups. Interestingly, aortic oxidative stress (lipid peroxides and isoprostane F(2alpha)-III contents) and NADPH oxidase component (p22phox and gp91phox) mRNA expression were increased in the HC group but not in the HC plus Flu group. The A23187-induced nitric oxide production from the aorta was increased in both HC and HC plus Flu groups. There was no significant difference in tissue endothelial-type nitric oxide synthase mRNA expression. Plaque area and intimal thickening of the aorta were significantly lowered in the HC plus Flu group. Flu treatment preserved the endothelial function associated with the decrease in markers of oxidative stress in this experiment. These beneficial endothelial effects of Flu are likely to occur independently of plasma lipid concentrations and to be mediated by its antioxidant action.

Animals↗

PubMed2006

Involvement of endothelial cell-derived CGRP in heat stress-induced protection of endothelial function.

Previous studies have shown that heat stress possesses cardioprotection, which is related to the synthesis and release of calcitonin gene-related peptide (CGRP) via activation of capsaicin receptor (vanilloid receptor subtype 1, VR1) on the capsaicin-sensitive sensory neurons. The VR1 exists in human umbilical vein endothelial cells (HUVECs). Endothelial cells can synthesize CGRP and CGRP could protect against endothelial dysfunction induced by lysophosphatidylcholine (LPC) or oxidized low-density lipoprotein. In the present study, we explored whether the endothelial cell-derived CGRP is involved in the effect of heat stress on endothelial function in vivo and in vitro. Our results indicated that heat stress significantly increased the plasma concentration of CGRP, which was abolished by pretreatment with capsazepine, a VR1 antagonist. Immunohistochemistry and in situ hybridization showed that the endothelium of mesenteric artery and aorta expressed CGRP. And heat stress increased the expression of CGRP, which was also abolished by capsazepine. LPC attenuated the endothelium-dependent relaxation responses of aorta rings, which were improved by pretreatment with heat stress. In cultured HUVECs, the CGRP secretion was increased after heat stress. LPC increased the lactate dehydrogenase (LDH) activity in the cultured medium and decreased the cell viability, suggesting that LPC injured the HUVECs. However, pretreatment with heat stress attenuated the injurious effects of LPC on HUVECs. And this beneficial effect of heat stress on HUVECs was inhibited by capsazepine or CGRP(8-37), the CGRP receptor antagonist. The present results suggest that the endothelial cell-derived CGRP contributes to the protective effects of heat stress on endothelial function. Our study provides a potential mechanism to explain the protective effect of heat stress on cardiovascular system.

Animals↗

PubMed2006

The effects of periodontal therapy on vascular endothelial function: a pilot trial.

BACKGROUND: Chronic periodontal infection is associated with an increased risk of coronary heart disease. Although the mechanism responsible for the relationship between periodontal disease and cardiovascular events is not fully understood, it is hypothesized that the chronic inflammatory burden of periodontal disease may lead to impaired functioning of the vascular endothelium. METHODS: Twenty-two otherwise healthy adults with moderate to severe periodontitis who underwent complete mouth disinfection were evaluated to determine if periodontal therapy would result in improved endothelial function and a decrease in serum inflammatory markers. Subjects had measurements of periodontal disease severity, flow-mediated (endothelium-dependent), and nitroglycerin-mediated (endothelium-independent) dilation of the brachial artery, serum C-reactive protein (CRP) and interleukin 6 (IL-6), and serum total and high-density lipoprotein cholesterol levels on 2 baseline visits separated by 1 month and, again, 1 month after treatment. RESULTS: There were no significant changes in clinical periodontal measures, flow-mediated dilation, nitroglycerin-mediated dilation, CRP, IL-6, total cholesterol, or high-density lipoprotein cholesterol between the repeated baseline measurements. Periodontal treatment, however, resulted in significant improvements in periodontal pocketing, flow-mediated dilation, and serum IL-6, as well as a trend toward reduction in serum CRP; there were no significant changes in nitroglycerin-mediated dilation or in cholesterol levels. CONCLUSIONS: These results represent proof of concept that improvement in endothelial function, as measured by flow-mediated dilation of the brachial artery, may be possible through near-elimination of chronic oral infection and suggest that the conduct of a larger controlled trial is justified.

Adult↗

PubMed2004

[Comparison of effects of taizhi' an capsule and pravastatin on vascular endothelial function in senile patients with coronary heart disease].

OBJECTIVE: To explore the anti-atherosclerosis effect of Taizhi'an Capsule (TZA) for providing a theoretical base of its application in preventing coronary heart disease (CHD), by way of observing the effects of TZA and pravastatin (PVT) on vascular endothelial function in senile patients with CHD. METHODS: Seventy-eight Senile patients with CHD were randomly divided into the TZA group and the PVT group, 39 in each group. Changes of carotid arterial intima-media thickness (IMT) and brachial arterial endothelium dependent diastolic function (FMD) before and after treatment were observed by non-invasive ultrasound test technique, and levels of serum nitric oxide (NO) and plasma endothelin-1 (ET-1) were determined as well. RESULTS: After TAZ treatment, IMT decreased from 1.21 +/- 0.17 mm to 0.91 +/- 0.13 mm, FMD increased from 5.02 +/- 0.58% to 8.97 +/- 0.39%, ET-1 lowered from 95.93 +/- 19.41 ng/L to 49.35 +/- 53.27 ng/L, and NO enhanced from 42.56 +/- 14.12 mumol/L to 69.84 +/- 21.96 mumol/L; after PVT treatment, the corresponding changes were 1.25 +/- 0.21 mm to 0.88 +/- 0.32 mm, 4.90 +/- 0.37% to 8.12 +/- 0.25%, 89.35 +/- 10.02 ng/L to 47.96 +/- 11.05 ng/L and 51.71 +/- 9.39 mumol/L to 72.93 +/- 16.51 mumol/L, all the changes were statistically significant. CONCLUSION: TZA can obviously improve the vascular endothelial function in old patients with CHD, which has the anti-atherosclerosis effect similar to that of PVT.

Aged↗

PubMed2004

Brachial artery endothelial function in residents and fellows working night shifts.

Brachial artery endothelial function, which is measured as responsiveness to reactive hyperemia (flow-mediated dilation [FMD]) was abnormal in residents and house staff after a 24-hour shift, including night duty. The greatest decrease in FMD was observed in physicians with a longer history of night-shift duty and in those reporting fewer sleeping hours during the shift. The finding that FMD is decreased after night duty raises the issue of the effects of shift duty on cardiovascular function in healthcare personnel, particularly in those undertaking night duty for a prolonged period of time.

Adult↗

PubMed2005

Effect of intensive versus moderate lipid lowering on endothelial function and vascular responsiveness to angiotensin II in stable coronary artery disease.

Recent evidence has demonstrated that intensive lipid-lowering therapy with a high-dose statin provides significant clinical benefit beyond moderate lipid-lowering therapy. However, dose-dependent effects of short-term statin therapy on vascular function have not been demonstrated. We studied endothelial function and vascular responsiveness to angiotensin II in patients who had coronary artery diseased and were randomized to receive low- or high-dose atorvastatin (10 or 80 mg, respectively) or placebo. Internal thoracic artery segments were obtained during coronary bypass surgery and studied in vitro. Endothelium-dependent vasodilation was increased with atorvastatin therapy (p = 0.035) but was significantly increased further in patients who received 80 mg compared with those who received 10 mg of atorvastatin (p = 0.05). Endothelium improvement was accompanied by decreased vascular response to angiotensin II (p = 0.039). These findings suggest a mechanism for the clinical benefit of intensive lipid-lowering treatment in coronary heart disease.

Aged↗

PubMed2004

Plasma antioxidant activity and cutaneous microvascular endothelial function in athletes and sedentary controls.

Aging is associated with endothelial dysfunction in both conduit arteries and peripheral microcirculation. Furthermore, aging is associated with an increased susceptibility to free radical mediated tissue damage. The aim of this study was to assess the relationship between age, regular aerobic-endurance training, plasma antioxidant activity and microcirculatory skin blood flow in healthy individuals. Thirty-six male athletes (range: 22-74 years; VO2max 54.3 +/- 5.2 ml/kg/min) and 36 age-sex-matched sedentary controls (range: 20-75 years; VO2max 34.2 +/- 3.4 ml/kg/min) were studied. Each group was divided into a younger (<30 years) and an older (>60 years) subgroup. Hand and foot baseline and stimulated skin blood flow (SBF) was measured by laser-Doppler flowmetry. Plasma free radicals antioxidant capacity against both peroxyl and hydroxyl radicals was also evaluated as Total Oxyradical Scavenging Capacity (TOSC) units. Baseline SBFs were not significantly different between athletes and sedentary groups, while plasma TOSC values against peroxyl radicals (18.4 +/- 3.1 vs. 13.8.0 +/- 3.4 units/ml, P < 0.001) and hydroxyl radicals (8.7 +/- 2.5 vs 4.9 +/- 2.3 units/ml, P <0.001) was higher in athletes. Hand SBF after heating and ischemia and foot SBF after heating were higher in athletes (P <0.0001) than in the sedentary group. In the sedentary groups, the lowest tertile of age had higher plasma TOSC values than the highest tertile of age (ROO- 18.2 +/- 2.2 vs 8.8 +/- 1.4 units/ml; HO- 9.2 +/- 1.3 vs 3.7 +/- 0.5 units/ml, P < 0.001). Among athletes, the lowest and the highest tertile of age did not show significantly different plasma TOSC (young: ROO- 20.3 +/- 1.5 and HO-: 9.7 +/- 1.4 units/ml; older: ROO-: 17.1 +/- 1.3 and HO-: 9.0 +/- 0.8 units/ml, n.s.). Resting SBF was similar in all the subgroups; stimulated SBFs were lower in both subgroups of untrained respect to trained individuals (P <0.001). In the sedentary subjects, SBF was inversely related to age (r = -0.63; P <0.0001) and directly related to TOSC against peroxyl (r = 0.59, P <0.001) and hydroxyl radicals (r = 0.47, P <0.01). In athletes SBF was related only to VO2max (r = 0.36; P <0.05) and TOSC vs ROO. (r = 0.41, P <0.01). In conclusion, these results suggest that regular physical activity is associated with a better microvascular endothelial function in older athletes probably due to increased antioxidant defenses.

Adult↗

PubMed1999

Angiotensin converting enzyme inhibition and arterial endothelial function in adults with Type 1 diabetes mellitus.

AIMS: Arterial endothelial dysfunction is a key early event in atherogenesis, and occurs in asymptomatic adults with Type 1 diabetes mellitus (DM). As angiotensin converting enzyme (ACE) inhibitors have been reported to reverse microvascular endothelial dysfunction acutely, we assessed the longer term effect of ACE inhibition on large vessel endothelial physiology in a randomized, crossover double-blind controlled clinical trial. METHODS: Flow-mediated arterial dilatation (FMD), which is largely due to endothelial release of nitric oxide, was assessed by vascular ultrasound in 20 Type 1 DM subjects with known endothelial dysfunction. These subjects, aged 28+/-5 years, were studied before and after 12 weeks oral therapy with either the ACE inhibitor perindopril 4 mg daily or the diuretic hydrene (triamterene 50 mg with hydrochlorothiazide 25 mg) daily. RESULTS: Although perindopril lowered both systolic and diastolic blood pressure by 2.7/3.2 mmHg, respectively (F3,78 = 4.7, P= 0.006; F3,78 = 3.2, P = 0.03), there was no significant effect of either perindopril or hydrene on FMD (baseline FMD before perindopril 4.6+/-2.5%, after 4.1+/-3.4%, baseline FMD before hydrene 5.4+/-3.6%, after 6.0+/-3.3%; F3,78= 1.9, P=0.1). Glycaemic control deteriorated slightly on hydrene whilst lipid levels, heart rate, resting blood flow and the arterial responses to nitroglycerine, a smooth muscle dilator, were unaffected by the treatment given. CONCLUSION: ACE inhibitor therapy for 3 months did not improve arterial endothelial function in Type 1 DM subjects.

Adult↗

PubMed2005

Opposite relationship between circulating soluble CD14 concentration and endothelial function in diabetic and nondiabetic subjects.

Recent prospective studies indicate endothelial dysfunction and increased risk for cardiovascular events in patients with serological evidence of multiple infections. Soluble CD14 (sCD 14) plays a key role in the neutralization of lipopolysaccharide (LPS), a well-established bacterial product inducing endothelial dysfunction. Insulin resistance was recently identified as a significant factor influencing circulating sCD 14 concentration. Thus, we investigated the association of circulating sCD14 and endothelial dysfunction in subjects with well-established insulin resistance (patients with type 2 diabetes, n = 40) compared to control non-diabetic subjects (n = 100). To further explore the underlying mechanisms, we also analysed C-reactive protein and circulating NO2-/NO3- and cyclic GMP in the diabetic group. Serum sCD 14 concentration (ELISA) was found to be differently associated with endothelium-dependent vasodilatation (EDVD, high-resolution ultrasound) in diabetic and non-diabetic subjects. In nondiabetic subjects, serum sCD14 and C-reactive protein correlated negatively with EDVD (r = -0.21, p = 0.03, and r = -0.21, p = 0.03, respectively). In a partial correlation analysis, these associations remained significant after controlling for age and weight (sCD 14 and EDVD, r = -0.23, p = 0.023; C-reactive protein and EDVD, r = -0.21, p = 0.03; sCD14 and C-reactive protein, r = 0.30, p = 0.002). In contrast, sCD 14 was positively associated with EDVD in type 2 diabetic patients (r = 0.37, p = 0.019,). Interestingly, sCD14 was also associated with NO2-/NO3- in this group (r = 0.62, p = 0.001, n = 22). EDVD also correlated with cyclic GMP (r = 0.47, p = 0.03, n = 22). In summary, circulating sCD 14 is associated with endothelial function. While in non-diabetic subjects sCD14 behaves as an acute phase reactant, its role in type 2 diabetic patients should be further clarified. These findings need to be confirmed in further studies with larger number of patients.

Brachial Artery↗

PubMed2001

Impairment of vascular endothelial function and left ventricular filling : association with the severity of apnea-induced hypoxemia during sleep.

STUDY OBJECTIVE: To investigate whether a dose-effect relationship exists between the severity of obstructive sleep apnea (OSA) and subclinical indicators of myocardial or vascular dysfunction. DESIGN: Cross-sectional study using correlation analysis. PARTICIPANTS: Twenty subjects referred to our sleep laboratory for screening or therapy of OSA but without regular medication and without known cardiovascular disease. MEASUREMENTS: Severity of OSA was quantified by polysomnography. Moreover, nocturnal excretion of norepinephrine was determined. Left ventricular (LV) myocardial function was assessed with Doppler echocardiography. Using ultrasonographic measurements, endothelium-dependent and endothelium-independent conduit artery dilation were measured as flow-mediated and glyceryltrinitrate-induced changes in brachial artery diameter. RESULTS: Worsening nocturnal hypoxemia, measured as nocturnal oxygen saturation nadir or percentage of sleep time spent in hypoxemia (< 90% hemoglobin oxygen saturation), predicted increased interventricular septum thickness (corrected for age and body mass index), prolonged isovolumetric relaxation time, decreased ratio between peak early and late mitral flow velocities, as well as reduced endothelium-dependent dilatory capacity of the brachial artery (all relationships corrected for cofactor age and with p < 0.05) were observed. Associations between these cardiovascular function markers and nocturnal excretion of norepinephrine followed the same trend, but relations with interventricular septum thickness and flow-mediated artery dilation missed significance (p = 0.064 and p = 0.061, respectively). LV posterior wall thickness, measures of LV systolic function, early mitral flow deceleration time, and endothelium-independent artery dilation were not significantly related to the degree of nocturnal hypoxemia or norepinephrine excretion. None of the correlations with apnea-hypopnea index were statistically significant. CONCLUSIONS: The severity of apnea-related hypoxemia is associated with a gradual deterioration of LV diastolic function as well as large-artery endothelial function.

Adult↗

PubMed2001

Effects of kidney-pancreas transplantation on atherosclerotic risk factors and endothelial function in patients with uremia and type 1 diabetes.

Cardiovascular disease and the development of coronary artery disease play a pivotal role in increasing mortality in patients with type 1 diabetes. The aim of our study was to evaluate the effects of pancreas transplantation on atherosclerotic risk factors, endothelial-dependent dilation (EDD), and progression of intima media thickness (IMT) in patients with uremia and type 1 diabetes after kidney-alone (KA) or kidney-pancreas (KP) transplantation. A cross-sectional study comparing two groups of patients with type 1 diabetes was performed. Sixty patients underwent KP transplantation and 30 patients underwent KA transplantation. Age and cardiovascular risk profile were comparable in patients before transplantation. In all patients, atherosclerotic risks factors (lipid profile, fasting and post-methionine load plasma homocysteine, von Willebrand factor levels, D-dimer fragments, and fibrinogen) were assessed and Doppler echographic evaluation of IMT and endothelial function with flow-mediated and nitrate dilation of the brachial artery was performed. Twenty healthy subjects were chosen as controls (C) for EDD. Compared with patients undergoing KA transplantation, patients undergoing KP transplantation showed lower values for HbA1c (KP = 6.2 +/- 0.1% vs. KA = 8.4 +/- 0.5%; P < 0.01), fasting homocysteine (KP = 14.0 +/- 0.7 mcromol/l vs. KA = 19.0 +/- 2.0 micromol/l; P = 0.02), von Willebrand factor levels (KP = 157.9 +/- 8.6% vs. KA = 212.5 +/- 16.2%; P < 0.01), D-dimer fragments (KP = 0.29 +/- 0.02 microg/ml vs. KA = 0.73 +/- 0.11 microg/ml;P < 0.01), fibrinogen (KP = 363.0 +/- 11.1 mg/dl vs. KA = 397.6 +/- 19.4 mg/dl; NS), triglycerides (KP = 122.7 +/- 8.6 mg/dl vs. KA = 187.0 +/- 30.1 mg/dl; P = 0.01), and urinary albumin excretion rate (KP = 13.5 +/- 1.9 mg/24 h vs. KA = 57.3 +/- 26.3 mg/24 h; P < 0.01). Patients undergoing KP transplantation showed a normal EDD (KP = 6.21 +/- 2.42%, KA = 0.65 +/- 2.74%, C = 8.1 +/- 2.1%; P < 0.01), whereas no differences were observed in nitrate-dependent dilation. Moreover, IMT was lower in patients undergoing KP transplantation than in patients undergoing KA transplantation (KP = 0.74 +/- 0.03 mm vs. KA = 0.86 +/- 0.09 mm; P = 0.04). Our study showed that patients with type 1 diabetes have a lower atherosclerotic risk profile after KP transplantation than after KA transplantation. These differences are tightly correlated with metabolic control, fasting homocysteine levels, lower D-dimer fragments, and lower von Willebrand factor levels. Normal endothelial function and reduction of IMT was observed only in patients undergoing KP transplantation.

Adult↗

PubMed2006

Clinical methods for the evaluation of endothelial function-- a focus on resistance arteries.

Endothelial dysfunction is a key event in the pathophysiology of cardiovascular diseases and appears as a strong independent predictor of cardiovascular events. In this context, biological evaluation of endothelial circulating markers can be helpful. However, functional tests using pharmacological stimuli appear more specific for the study of resistance arteries. These methods consist in the evaluation of the endothelium-dependent changes in regional vascular flow in response to local infusion of substances that act through endothelial receptors without modification of systemic arterial pressure and in comparison with a non endothelium-dependent relaxation. Flow is measured by Doppler and intravascular ultrasound in coronary circulation, laser Doppler in skin and by venous occlusion plethysmography in peripheral muscular arteries. Similar studies can be performed ex vivo using isolated resistance arteries obtained from fat subcutaneous biopsies. In addition, other information can be obtained from reactive hyperemia and the study of the flow-mediated dilatation of conduit arteries to enable a selective and comprehensive approach of the heterogeneity of endothelial function in pathophysiology.

Acetylcholine↗

PubMed2005

Divergent effects of rofecoxib on endothelial function and inflammation in acute coronary syndromes.

BACKGROUND: The safe use of selective inhibitors of cyclooxygenase-2 in patients with cardiovascular disease has been questioned because of studies showing an increased risk of cardiac events. We examined the short-term effect of rofecoxib, a selective cyclooxygenase-2 inhibitor, on endothelial function, oxidative damage and inflammation in patients with acute coronary syndromes without ST-segment elevation. METHODS: Forty-three patients with acute coronary syndromes without ST-segment elevation participated in the study. Flow-mediated dilatation (FMD), nitrate-mediated dilatation (NMD) of the brachial artery, malondialdehyde, a marker of lipid peroxidation, C-reactive protein, an acute phase marker of inflammation, and interleukin-6, a proinflammatory cytokine, were measured within 24 h of admission and a week later. Patients were randomized to receive for a week 100 mg aspirin daily with either 25 mg of rofecoxib (n=21) or placebo (n=22) orally once daily. RESULTS: Malondialdehyde, C-reactive protein and interleukin-6 levels were reduced in the rofecoxib group (p=0.04, p=0.003 and p=0.02 respectively) while they remained unchanged in the placebo group after 1 week of treatment. FMD and NMD changes in both groups were not statistically different. CONCLUSIONS: Co-administration of rofecoxib with low-dose aspirin decreases inflammatory and oxidative indices but does not improve endothelial function. The lack of improvement in FMD despite the improvement in inflammation and oxidative stress could be viewed in association to the recent observations on the adverse effects of COX-2 inhibition on the cardiovascular system.

Acute Disease↗

PubMed2002

Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality. Striking similarities exist in the inflammatory and immunologic response in RA and atherosclerosis. Indeed, adhesion molecules and cytokines, tumor necrosis factor (TNF)-alpha in particular, are key mediators of joint inflammation and of vascular dysfunction and progression of atherosclerotic vascular disease. Hence, the aim of the present study was to assess the effect of chronic antiinflammatory treatment with the anti-TNF-alpha antibody infliximab on disease activity and endothelial function in patients with active RA. METHODS AND RESULTS: Eleven RA patients (mean age 46+/-5 years; disease duration 9+/-2 years) with high disease activity despite treatment with stable doses of methotrexate (<or=25 mg/wk) and prednisone (<or=10 mg/d) were investigated. Clinical status and endothelium-dependent and -independent vasodilation of the brachial artery as assessed by high-resolution ultrasound were measured before and after 12 weeks of infliximab therapy. Flow-mediated vasodilation improved from 3.2+/-0.4% to 4.1+/-0.5% (P=0.018), whereas endothelium-independent vasodilation with nitroglycerin and baseline diameter remained unchanged (13.6+/-1.2% versus 12.8+/-1.4%, P=0.98, and 3.74+/-0.15 versus 3.66+/-0.11 mm, P=0.54, respectively). Disease activity score (DAS28) was significantly reduced, from 5.6+/-0.3 to 3.5+/-0.6 (P=0.002). Erythrocyte sedimentation rate and C-reactive protein were lowered from 34+/-7 to 19+/-5 mm/h (P=0.04) and from 38+/-11 to 15+/-10 mg/L (P=0.08), respectively. CONCLUSIONS: This is the first study to show that anti-TNF-alpha treatment improves endothelial function in RA. The data suggest that in RA, endothelial dysfunction is part of the disease process and is mediated by TNF-alpha.

Antibodies, Monoclonal↗

PubMed1999

Impaired brachial artery endothelial function is not predicted by elevated triglycerides.

OBJECTIVES: The purpose of this study was to determine if patients with modest hyperlipidemia, and no other risk factors for coronary artery disease (CAD), have impaired endothelium-dependent (ED) vasoactivity. BACKGROUND: Hypercholesterolemia impairs ED vasodilation, but the impact of elevated triglycerides on endothelial function is not as well established. METHODS: High-resolution ultrasound was used to determine flow-mediated dilation (FMD) in the brachial artery (BA) after a 5-min arterial occlusion (endothelium-dependent stimulus) and nitroglycerin-induced dilation (endothelium-independent stimulus). We studied 40 healthy controls (Group 1), 38 patients with elevated low-density lipoprotein (LDL) cholesterol (Group 2) and 35 patients with elevated triglycerides (Group 3). Patients were excluded if they had known CAD or other risk factors for CAD, or if they were receiving lipid-lowering or vasoactive medications. RESULTS: Control patients (Group 1) had normal LDL cholesterol (2.6+/-0.8 mmol/liter) and triglyceride levels (1.0+/-0.5 mmol/liter) compared with Group 2 (5.2+/-1.2 mmol/liter, 1.8+/-0.6 mmol/liter) and Group 3 (3.5+/-0.9 mmol/liter, 4.2+/-2.5 mmol/liter) subjects (p < 0.001). Baseline BA diameters were the same across the three groups. There was no significant attenuation of flow-mediated vasodilation (FMD) in either of the hyperlipidemic groups (Group 1: 10.9+/-5.0% vs. Group 2: 8.6+/-6.1% vs. Group 3: 9.4+/-3.9%; p = 0.14). However, nitroglycerin-induced vasodilation was mildly reduced (Group 1: 21.0+/-5.0% vs. 16.9+/-7.6% vs. 17.3+/-7.7%; p = 0.01). By multivariate analysis, after controlling for baseline diameters, only the ratio of LDL/high-density lipoprotein predicted a minor impairment in FMD. CONCLUSIONS: In patients free from other cardiac risk factors, modest elevations of triglycerides or LDL cholesterol do not significantly attenuate BA endothelial-dependent vasodilation. Synergism with other cardiac risk factors may be required to significantly impair endothelial function in these patients.

Adult↗

PubMed2005

Impaired endothelial function in patients with ankylosing spondylitis.

OBJECTIVE: In recent years, accelerated atherosclerosis and increased risk of cardiovascular events have been described in patients with rheumatic disease, particularly for rheumatoid arthritis and systemic lupus erythematosus. However, the link between inflammation, atherosclerosis and ankylosing spondylitis is controversial. We evaluated the degree of atherosclerosis and endothelial function of ankylosing spondylitis patients ultrasonographically. METHODS: Fifty-four patients with ankylosing spondylitis (37 +/- 11 yr, 29 males, 25 females) and 31 healthy controls (35 +/- 9 yr, 16 males, 15 females) were consecutively enrolled in the study. Serum lipids, creatinine, glucose, and acute-phase proteins were assessed. The Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were also evaluated. Flow-mediated dilatation and endothelium-independent dilatation of the brachial artery and intima-media thickness of the common carotid artery were measured sonographically. RESULTS: Left, right and averaged intima-media thickness of the common carotid artery did not show a statistically significant difference between the ankylosing spondylitis and control groups. However, flow-mediated dilatation was significantly lower in the ankylosing spondylitis patients (14.1 +/- 6.7 vs 17.6 +/- 8%; P = 0.03). Likewise, nitroglycerin-induced dilatation was lower in the patient group, but the difference was not significant (16.4 +/- 6.8 vs 19.8 +/- 10%; P = 0.07). No correlation was detected between flow-mediated dilatation and age, sex, serum lipids, CRP, ESR, smoking habits and disease activity scores. Intima-media thickness of the common carotid artery was positively correlated with age and BASMI score (r = 0.55, P = 0.00; r = 0.22, P = 0.04, respectively). CONCLUSION: This study demonstrates impairment of endothelial function in ankylosing spondylitis.

Adult↗

PubMed1997

Superiority of hyperpolarizing to depolarizing cardioplegia in protection of coronary endothelial function.

OBJECTIVE: Hyperpolarizing cardioplegia has recently been proposed for myocardial protection. To compare the protective effect of hyperpolarizing cardioplegia and depolarizing (hyperkalemic) cardioplegia on coronary endothelium, we studied porcine coronary arteries in the organ chamber. METHODS: Relaxation mediated by the endothelium-derived hyperpolarizing factor (EDHF) was used as the index of endothelial function because (1) hyperkalemia without ischemia does not impair the nitric oxide-mediated function according to previous studies and (2) EDHF relaxes vessels by hyperpolarizing the membrane potential. Therefore depolarizing cardioplegia may inhibit this function, but hyperpolarizing cardioplegia may preserve it. EDHF-mediated relaxation was induced by bradykinin and the calcium ionophore A23187 with the presence of indomethacin (7 micromol/L; INN: indometacin), a cyclooxygenase inhibitor, and N(G)-nitro-L-arginine (300 micromol), a nitric oxide biosynthesis inhibitor in U46619 (30 nmol/L)-induced precontraction. The vessels were exposed to either hyperpolarizing cardioplegic solution (the potassium-channel opener aprikalim, 0.1 mmol/L) or depolarizing cardioplegic solution (high potassium concentration, 20 mmol/L for A23187 and 50 mmol/L for bradykinin experiments) for 1 hour with a constant supply of oxygen to exclude the effect of ischemia. RESULTS: EDHF-mediated relaxation was significantly impaired in either A23187 or bradykinin studies (80.1% +/- 7.5% vs 24.9% +/- 14.2%, p = 0.004, n = 8 in each group for A23187, and 71.4% +/- 4.7%, n = 13, vs 40.5% +/- 12.9%, n = 7, p = 0.01, for bradykinin). The effective concentration causing 50% of maximal relaxation was significantly increased in the A23187 experiments with the treatment of hyperkalemia. In contrast, in aprikalim-treated arteries, the EDHF-mediated relaxation induced by either A23187 or bradykinin was unchanged. CONCLUSIONS: We conclude that EDHF-mediated coronary endothelial function is maximally preserved by hyperpolarizing cardioplegia but impaired by depolarizing cardioplegia. These findings support the use of hyperpolarizing cardioplegia in cardiac operations.

Animals↗