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At least 1,333 records · Page 74Linked to original sources
PubMed2006

Is reversal of endothelial dysfunction by tea related to flavonoid metabolism?

Dietary flavonoids can improve endothelial function, but the response varies between individuals. Wide variability is also seen in flavonoid O-methylation, a major pathway of flavonoid metabolism. The O-methylation of flavonoids could alter activity, and thus influence any effect on endothelial function. The objective of the current analysis was to investigate whether variability in the endothelial function response to ingestion of tea, a rich source of flavonoids, is related to the degree of O-methylation of flavonoids. This relationship was investigated in two studies in which endothelium-dependent flow-mediated dilatation (FMD) of the brachial artery was assessed and urinary 4-O-methylgallic acid (4OMGA) excretion was used as a marker of the O-methylation of tea-derived flavonoids. In the first study, amongst participants consuming five cups of tea per day for 4 weeks, the degree of increase in 4OMGA excretion was inversely associated with the change in FMD responses (r -078, P=0.008). In the second study, there was a significant difference in the FMD responses to acute ingestion of three cups of tea between individuals with a low ( median) 4OMGA response (1.94 (sem 0.79) % and -0.25 (sem 0.53) %, respectively; P=0.03). That is, any improvement in FMD following ingestion of tea may be enhanced in individuals who O-methylate less of the absorbed flavonoids. The present results are consistent with the suggestion that differences in flavonoid metabolism may influence their effect on endothelial function. Thus, differences in flavonoid metabolism could be related to the level of benefit of dietary flavonoids on the risk of CVD.

Brachial Artery↗
PubMed2006

Endothelial dysfunction in cold type complex regional pain syndrome.

The authors examined endothelial function in cold type chronic complex regional pain syndrome (CRPS) I using acetylcholine- and sodium nitroprusside-induced vasodilation combined with laser Doppler flowmetry in 14 patients and 10 controls. On the affected side, acetylcholine-induced vasodilation was significantly reduced in comparison to controls and the unaffected extremity. No significant differences were found after application of sodium nitroprusside. The results demonstrate impaired endothelial function in chronic CRPS I.

Acetylcholine↗
PubMed2000

Lipid-mediated endothelial dysfunction: a common factor to preeclampsia and chronic vascular disease.

Preeclampsia is a complex pathophysiological state where regulatory systems of inflammation and endothelial function are stimulated beyond the physiological limits of normal pregnancy. Different lines of evidence indicate that abnormal lipid metabolism is not a mere manifestation but is also involved in the pathogenesis of the disease. Lipid-mediated oxidative stress is likely to contribute to endothelial hyperstimulation leading to dysfunction and damage. Maternal predisposing factors seem to be essential to explain why some pregnant women develop a systemic syndrome such as preeclampsia and why others do not. Preliminary evidence suggests that abnormal lipid metabolism could be one of these factors. In this review the evidence for the contribution of lipid oxidation in the pathogenesis of preeclampsia, the similarities between preeclampsia and lipid-mediated chronic vascular disease will be summarized, and the reasons to believe that constitutional lipid abnormalities could be one of the maternal predisposing factors for developing the disease will be examined and will be discussed.

Endothelium↗
PubMed2006

Effect of interaction between left ventricular dysfunction and endothelial function in hypertension.

Hypertension, one of the most important risk factors for cardiovascular diseases, is associated with both left ventricular hypertrophy and endothelial dysfunction. Both have been recently recognized as independent predictors of clinical events in different groups of patients. In fact, a dysfunctioning endothelium loses its antiatherosclerotic and antithrombotic action, and, therefore, promotes the atherosclerotic process. Similarly, cardiac hypertrophy is recognized as a powerful and independent risk factor for cardiovascular morbidity and mortality because it predisposes to arrhythmias and maximizes the consequences of acute myocardial ischemia. Recently, an evident interaction has been demonstrated between endothelial dysfunction and left ventricular mass. In particular, the coexistence of both left ventricular hypertrophy and endothelial dysfunction almost doubles the risk for future vascular events in hypertensives. Thus, in hypertensive patients, it is clinically useful to choose an aggressive therapeutic strategy--to reduce left ventricular mass and to improve endothelial function.

Coronary Artery Disease↗
PubMed2000

Atherogenic lipids and endothelial dysfunction: mechanisms in the genesis of ischemic syndromes.

Atherogenic lipids, particularly oxidized low-density lipoprotein, are responsible for a wide range of cellular dysfunctions within the vessel wall. The effects on endothelial cells disrupt normal control of vasomotion, with a reduction of effective nitric oxide activity, the development of a procoagulant surface, chronic low-grade inflammation, and abnormal cell growth. These changes are central not only in the development of atherosclerosis but also in the evolution of both stable and unstable ischemic syndromes. There is growing evidence that these abnormal changes in cell function respond rapidly to changes in the atherogenic lipids. Certain cell functions can improve within hours or days of cholesterol lowering.

Arteriosclerosis↗
PubMed2002

Serum non-esterified very long-chain PUFA are associated with markers of endothelial dysfunction.

The objective of this study was to investigate the pattern of serum non-esterified fatty acid (NEFA) fraction in association with atherosclerosis development. We have studied possible relationships between eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) in the NEFA fraction and biochemical markers of endothelial activation or dysfunction. The study population consisted of 152 elderly men with high risk for coronary heart disease. The composition of fasting serum NEFA was analysed by gas-liquid chromatography. Endothelial activation was evaluated using biochemical analyses of some markers of endothelial function. A significant inverse linear association was found between serum non-esterified EPA and DHA, and soluble vascular cell adhesion molecule-1 (sVCAM-1) (P=0.02 and 0.001, respectively). An inverse linear association was found between serum non-esterified AA and sVCAM-1 (P=0.001) and von Willebrand Factor (P=0.005). The significant inverse associations for DHA and AA were independent from the serum content of other NEFAs. Taken together, negative associations were found between sVCAM-1 and the serum levels of non-esterified DHA, EPA and AA. The inverse relation between the levels of sVCAM-1 and very long-chain n-3 fatty acids might indicate an anti-inflammatory effect of the latter.

Aged↗
PubMedDate not supplied

Endothelial dysfunction and coronary risk reduction.

There is growing evidence that improvement of endothelial function has the potential to reduce cardiovascular ris. This article reviews the impact of coronary risk factors on endothelial function and the benefits of risk factor reduction. Recent studies indicate that chronic exercise may directly improve endothelial function, thus providing an additional explanation for the benefits of increased physical activity.

Acute Disease↗
PubMed2003

Angiogenesis, thrombogenesis, endothelial dysfunction and angiographic severity of coronary artery disease.

BACKGROUND: Thrombogenesis, angiogenesis, and endothelial damage/dysfunction are components in the pathogenesis of atherosclerosis. OBJECTIVE: To investigate the relation of these variables to atherosclerotic disease severity and the possible interrelations between the three. METHODS: 111 patients attending for coronary angiography were studied (85 male, 26 female; mean (SD) age, 61.6 (10.0) years). Plasma concentrations of von Willebrand factor (vWf, a marker of endothelial damage/dysfunction), vascular endothelial growth factor (VEGF, associated with angiogenesis), soluble VEGF receptor Flt-1 (sFlt-1), and tissue factor (TF, a key component of coagulation) were measured by an enzyme linked immunosorbent assay. Following angiography, disease severity was assessed by the number of coronary vessels diseased (> 50% stenosis) and by a coronary atheroma score. RESULTS: All indices were raised in the patients compared with 34 healthy controls except sFlt-1, which was lower in the patients. No significant correlations were found between the coronary atheroma score and values of vWf (Spearman correlations: r = 0.21, p = 0.83), VEGF (r = 0.11, p = 0.27), or TF (r = -0.04, p = 0.68). However, there was an inverse correlation between plasma sFlt-1 and coronary atheroma score (r = -0.19, p = 0.049). The number of vessels diseased had no relation to any marker. Correlations were found between TF and VEGF (r = 0.25, p = 0.008) and between TF and sFlt-1 (r = 0.42, p < 0.001) in the patients. CONCLUSIONS: Despite evidence of abnormal angiogenesis (VEGF and sFlt-1), thrombogenesis (TF), and endothelial damage/dysfunction (vWf) in the patients with coronary artery disease, there was no correlation between VEGF, sFlt-1, vWf, or TF and angiographically defined disease severity.

Coronary Angiography↗
PubMed2001

Superoxide excess in hypertension and aging: a common cause of endothelial dysfunction.

There is evidence in humans that hypertension and aging similarly impair endothelial function, although the mechanism remains unclear. Superoxide anion (O(2)(-)) is a major determinant of nitric oxide (NO) bioavailability and thus endothelial function. We sought to determine the relationship between endothelial function, O(2)(-), and age in normotensive Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Aortic rings were removed from female WKY and SHRSP at 3 to 4 months (young) and 9 to 12 months (old). O(2)(-) generation by aortic rings was measured before and after removal of the endothelium or incubation with N(G) nitro-L-arginine methyl ester, diphenyleneiodonium, or apocynin. Levels of p22phox were studied with immunohistochemistry and used as a marker of NAD(P)H oxidase expression. NO bioavailability was significantly lower in old WKY compared with young WKY (P=0.0009) and in old SHRSP compared with young SHRSP (P=0.005). O(2)(-) generation was significantly greater in old WKY compared with young WKY (P=0.0001). Removal of the endothelium and N(G) nitro-L-arginine methyl ester treatment resulted in a significant reduction in O(2)(-) generation in old SHRSP (P=0.009 and 0.001, respectively). Diphenyleneiodonium significantly reduced O(2)(-) generation in 12-month WKY (P=0.008) and 12-month SHRSP (P=0.009). Apocynin attenuated O(2)(-) generation by older WKY (P=0.038) and SHRSP (P=0.028). p22phox was increased in older animals compared with young. We conclude that NO bioavailability decreases with age in female WKY and SHRSP. O(2)(-) generation increases with age in WKY and is higher in SHRSP and may contribute to the reduced NO by scavenging. NAD(P)H oxidase may contribute to the age-related increase in O(2)(-).

Acetophenones↗
PubMed1998

Vascular endothelial dysfunction contributes to myocardial depression in ischemia-reperfusion in the rat.

Endocardial and vascular myocardial capillary endothelium has been shown to modulate the contractile characteristics of myocardium by altering myofibrillar affinity for calcium. Although the release of endothelial-derived substances that modify myocardial contractility has been shown to be altered in certain physiologic and pathologic situations, until now no study has evaluated whether the direct modulatory effects of endothelium on its subjacent myocardium were altered in pathologic situations and contributed to loss of contractile function. This study was designed to evaluate whether the direct contractile modulatory effects of endocardial and (or) vascular endothelium were altered and whether these alterations contributed to contractile dysfunction in a model of ischemia-reperfusion. Sixty-two perfused rat hearts as Langendorff preparations were randomized to no intervention, intracoronary Triton X100 injection (to render vascular endothelium dysfunctional), ischemia (30 min)-reperfusion (20 min), and ischemia-reperfusion followed by intracoronary Triton X100 injection. Coronary endothelial-dependent vascular reactivity and vascular smooth muscle reactivity were assessed by serotonin and sodium nitroprusside, respectively. Myocardial damage was assessed by coronary effluent creatine phosphokinase and by morphologic studies. Papillary muscles were then excised and contractile characteristics evaluated at varying extracellular calcium concentration prior to and after endocardial endothelial removal with Triton X100. All three interventions eliminated all coronary vascular response to serotonin but did not modify response to nitroprusside. Creatine phosphokinase values rose only in hearts with ischemia-reperfusion, and only minor morphologic changes occurred, mostly in hearts with ischemia-reperfusion. Papillary muscles from hearts with intracoronary Triton X100 injection had lower contractile indices compared with normal controls (total tension 4.0 vs. 4.6 g/mm2, p < 0.01) and an abbreviation of contraction duration. Increasing extracellular calcium concentration from to 0.7 to 3.25 mM eliminated these differences. Similar but more marked decreases in contractile indices and twitch duration were noted in the two ischemia-reperfusion groups, but consistent with some myocardial damage being present, increasing extracellular calcium concentration to 3.25 or 7 mM did not fully eliminate these differences. In both ischemia-reperfusion groups and the intracoronary Triton X100 group, the relative increase in total tension with increasing extracellular calcium concentrations was similar (35 to 38%) and greater than that of the control group (25%), consistent with dysfunction of vascular endothelium contributing to myocardial dysfunction in the three intervention groups. Endocardial endothelial removal had a similar effect in all four groups, suggesting that dysfunction of endocardial endothelium does not play a role in this model. We conclude that vascular but not endocardial endothelial dysfunction contributes to the myocardial dysfunction that occurs during ischemia-reperfusion injury.

Animals↗
PubMed1999

Age-related progressive brachial artery endothelial dysfunction precedes the changed carotid and left ventricular geometry in healthy humans.

In this study the authors evaluated correlation between aging and brachial endothelial and vascular smooth muscle dysfunction, changes in carotid geometry, and left ventricular remodeling. Vasomotor influences of brachial endothelium and brachial smooth muscle function to reactive hyperemia and nitroglycerin (400 microg, sublingual spray) were assessed by noninvasive ultrasound in 66 healthy subjects of different ages (20-82 years). Carotid intima-media thickness and left ventricular mass index were also assessed by ultrasound and compared with brachial hemodynamic parameters. All results were analyzed by linear regression analysis. The response of brachial artery diastolic diameter to reactive hyperemia decreased with aging (p<0.0001). Also, the response of brachial artery diastolic diameter to nitroglycerin increased relative to aging (p<0.004). Age-related correlations between increased carotid intima-media thickness and brachial artery diastolic diameter response to reactive hyperemia (p<0.01) as well as between increased carotid intima-media thickness and increased left ventricular mass index (p<0.001) were found. However, there was no correlation between brachial artery diastolic diameter response to reactive hyperemia and increased left ventricular mass index (p>0.05). The study showed that aging influences not only brachial endothelial vasomotor properties but also vascular and cardiac geometry. The authors believe that modern therapeutic approach should take these results into consideration to establish new vasculo-protective and cardioprotective strategies.

Adult↗
PubMed1995

Is endothelial dysfunction reversible?

To date, the published database concerning the impact of therapy on endothelial function in essential hypertension and hypercholesterolemia is small and incomplete. Chronic antihypertensive therapy had not yet been proven to restore endothelial function in patients with essential hypertension. In contrast, chronic lipid-lowering therapy is effective in restoring endothelial function of the coronary and peripheral circulation in patients with hypercholesterolemia. A beneficial effect was already documented after 3 months of therapy with fluvastatin but full restoration may last more than 1 year.

Anticholesteremic Agents↗
PubMed2003

Nitrate tolerance and the links with endothelial dysfunction and oxidative stress.

Identification of nitric oxide as the molecule responsible for endothelial dependant vasodilatation has led to an explosion of interest in endothelial function. Oxidative stress has been identified as an important factor in the development of tolerance to organic nitrates. This review examines the evidence supporting this recently developed theory and how mechanisms of nitrate tolerance may link with the wider picture of primary nitric oxide resistance.

Arginine↗
PubMed1998

Endothelial dysfunction in preeclampsia.

Several years ago the hypothesis was advanced that alterations of endothelial function could explain much of the pathophysiology of preeclampsia. Since that time, extensive data have been generated to support the hypothesis. Markers of endothelial activation can be demonstrated in women with overt preeclampsia. More importantly, many of these markers precede clinically evident disease and disappear with resolution of the disease. The original postulate was that materials produced by the poorly perfused placenta, which is characteristic of preeclampsia, entered the systemic circulation and altered endothelial cell activity. This was proposed to change vascular sensitivity to circulating pressors, activate coagulation, and reduce vascular integrity resulting in the pathophysiological changes of preeclampsia. As data have accumulated it has become increasingly evident that the insult to the endothelium is neither toxicity nor nonspecific injury but rather can better be characterized as endothelial activation. Candidate molecules have been suggested but not established. It seems likely that the responsible agent(s) will not be unique molecules but rather usual molecules present in excessive amounts. The hypothesis has been expanded to invoke involvement of the maternal constitution in the generation of endothelial injury and injurants. This concept is stimulated by the observation that reduced placental perfusion per se is not sufficient to generate the maternal syndrome. Women with growth-restricted fetuses frequently are not preeclamptic. Placental bed biopsies from not only growth-restricted but also prematurely born infants demonstrate failure of the physiological remodeling of decidual vessels responsible for the reduced placental perfusion of preeclampsia. This has led to the concept that preeclampsia is secondary to an interaction of reduced placental perfusion and maternal factors. Interestingly these maternal factors, obesity, insulin resistance, black race, hypertension, and elevated plasma homocysteine concentration are all risk factors for atherosclerosis in later life.

Biomarkers↗
PubMed1996

Preconditioning prevents chronic reperfusion-induced coronary endothelial dysfunction in rats.

Experiments were designed to test whether preconditioning protects against chronic endothelial injury after ischemia and reperfusion. Coronary arteries were isolated from rats subjected to sham surgery or 20 min of ischemia followed by 1 h, 1 day, 1 wk, or 1 mo of reperfusion without or with preconditioning. The endothelium-dependent relaxations to acetylcholine (ACh; assessed in vitro) were markedly reduced after ischemia and 1 h of reperfusion (31 +/- 6 vs. 57 +/- 6% in sham; P < 0.01) and did not recover after longer durations of reperfusion (1 mo: 32 +/- 5 vs. 56 +/- 2%; P < 0.01). The impaired response to ACh was restored by preconditioning at all time points (1 h: 53 +/- 6; 1 mo: 65 +/- 4%). After 1 mo, the potency of ACh in preconditioned arteries was also increased compared with that in sham animals. Electron microscopy showed marked endothelial damage after 1 h of reperfusion and signs of regenerated endothelium after 1 mo of reperfusion. Both acute and chronic ultrastructural changes were prevented by preconditioning. Thus preconditioning, in addition to protecting myocardial cells, also protects against chronic reperfusion-induced endothelial injury, both in terms of functional and structural changes.

Acetylcholine↗
PubMed2005

Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia.

OBJECTIVE: Improvement in endothelial function is predicted to improve insulin sensitivity, and this may be one mechanism by which fenofibrate decreases the incidence of coronary heart disease. We hypothesize fenofibrate improves endothelial function by enhancing insulin sensitivity. RESEARCH DESIGN AND METHODS: We administered placebo or fenofibrate 200 mg daily for 8 weeks to 46 patients with primary hypertriglyceridemia (24 had metabolic syndrome). This study was randomized, double blind, placebo controlled, and crossover in design. RESULTS: Compared with placebo, fenofibrate decreased total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides and increased HDL cholesterol and apolipoprotein A-I (all P < 0.001) while tending to decrease LDL cholesterol (P = 0.069). Fenofibrate significantly improved percent flow-mediated dilator response to hyperemia by 48 +/- 5% (P < 0.001) and lowered plasma levels of high-sensitivity C-reactive protein (hsCRP) relative to baseline measurements from 0.80 to 0.70 mg/l (P = 0.001) and fibrinogen levels by 16 +/- 3% (P < 0.001). Compared with placebo, fenofibrate therapy significantly increased plasma levels of adiponectin by 14 +/- 5% (P = 0.008) and increased insulin sensitivity (assessed by quantitative insulin sensitivity check index [QUICKI]) by 6 +/- 2% (P = 0.048). There were significant correlations between percent changes in adiponectin levels and percent changes in flow-mediated dilation (r = 0.401, P = 0.006), hsCRP (r = -0.443, P = 0.002), or QUICKI (r = 0.292, P = 0.049). Multivariate regression analysis showed that only changes in adiponectin levels persisted as an independent predictor of changes in flow-mediated dilation (r = 0.504, P = 0.013). Overall, we observed similar results in 24 patients with metabolic syndrome. CONCLUSIONS: Fenofibrate therapy significantly improved percent flow-mediated dilator response to hyperemia, reduced inflammation marker levels, increased adiponectin levels, and improved insulin sensitivity in hypertriglyceridemic or metabolic syndrome patients.

Adiponectin↗
PubMed2005

NAD(P)H oxidase contributes to the progression of remote hepatic parenchymal injury and endothelial dysfunction, but not microvascular perfusion deficits.

Oxidative stress occurs in remote liver injury, but the origin of the oxidant generation has yet to be thoroughly delineated. Some reports suggest that the source of the distant oxidative stress originates from the site of initial insult [i.e., xanthine oxidase (XO)]; however, it could also be derived from sources such as phagocytic and/or vascular NAD(P)H oxidase (Nox) enzymes. With a murine model of bilateral hindlimb ischemia-reperfusion, we describe here a mechanism for Nox-dependent oxidant production that contributes, at least in part, to remote hepatic parenchymal injury and sinusoidal endothelial cell (SEC) dysfunction. To determine whether Nox enzymes were the source of oxidants, mice were treated immediately after the onset of hindlimb ischemia with specific inhibitors to XO (50 mg/kg ip allopurinol) or Nox (10 mg/kg ip gp91ds-tat and 3 mg/kg ip apocynin). After 1 h of ischemia, hindlimbs were reperfused for either 3 or 6 h. Inhibition of XO failed to provide any improvement in parenchymal injury, SEC dysfunction, neutrophil accumulation, or microvascular dysfunction. In contrast, the inhibition of Nox enzymes prevented the progression (6 h) of parenchymal injury, significantly protected against SEC dysfunction, and completely prevented signs of neutrophil-derived oxidant stress. At the same time, however, inhibition of Nox failed to protect against the early parenchymal injury and microvascular dysfunction at 3 h of reperfusion. These data confirm that microvascular perfusion deficits are not essential for the pathogenesis of remote hepatic parenchymal injury. The data also suggest that Nox enzymes, not XO, are involved in the progression of compromised hepatic parenchymal and endothelial integrity during a systemic inflammatory response.

Animals↗