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PubMed2005

Protection of endothelial function.

The vascular endothelium synthesizes and releases a spectrum of vasoactive substances and therefore plays a fundamental role in the basal and dynamic regulation of the circulation. Nitric oxide (NO)--originally described as endothelium-derived relaxing factor--is released from endothelial cells in response to shear stress produced by blood flow, and in response to activation of a variety of receptors. After diffusion from endothelial to vascular smooth muscle cells, NO increases intracellular cyclic guanosine-monophosphat concentrations by activation of the enzyme guanylate cyclase leading to relaxation of the smooth muscle cells. NO has also antithrombogenic, antiproliferative, leukocyte-adhesion inhibiting effects, and influences myocardial contractility. Endothelium-derived NO-mediated vascular relaxation is impaired in spontaneously hypertensive animals. NO decomposition by free oxygen radicals is a major mechanism of impaired NO bioavailability. The resulting imbalance of endothelium-derived relaxing and contracting substances disturbs the nor- mal function of the vascular endothelium. Endothelin acts as the natural counterpart to endothelium-derived NO. In man, besides its effect of increasing arterial blood pressure, ET-1 induces vascular and myocardial hypertrophy, which are independent risk factors for cardiovascular morbidity and mortality. Current therapeutic strategies concentrate mainly on lowering of low-density lipoprotein cholesterol and an impressive reduction in the risk for cardiovascular morbidity and mortality has been achieved. Inflammatory mechanisms play an important role in vascular disease and inflammatory plasma markers correlate with prognosis. Novel therapeutic strategies specifically targeting inflammation thus bear great potential for the prevention and treatment of atherosclerotic vascular disease.

Adrenergic beta-Antagonists↗
PubMed2006

Differential expression of prokineticin receptors by endothelial cells derived from different vascular beds: a physiological basis for distinct endothelial function.

Prokineticins (PKs), multifunctional secreted proteins, activate two endogenous G protein-coupled receptors (R) termed PK-R1 and PK-R2. It was suggested that PK1 acts selectively on the endothelium of endocrine glands, yet PK-Rs were also found in endothelial cells (EC) derived from other tissues. Therefore we examined here the characteristics of PK - system in EC derived from different vascular beds. Corpus luteum (CL)-derived EC (LEC) expressed both PK-R1 and PK-R2. In contrast, EC from the aorta (BAEC) only expressed PK-R1. Interestingly, also EC from brain capillaries (BCEC) expressed only PK-R1. The distinct pattern of PK-R expression may define EC phenotypic heterogeneity. Regulation of receptor expression also differed in BAEC and LEC: TNFalpha markedly reduced PK-R1 only in BAEC, but serum removal decreased PK-R1 in both cell types. Therefore, if cells were initially serum-starved, the anti-apoptotic effect of PKs was retained only in LEC. Yet, addition of PKs concomitant with serum removal enhanced the proliferation and survival of both BAEC and LEC. Immunohistochemical staining showed that in CL and aorta PK1 was expressed in smooth muscle cells in vessel walls, suggesting a paracrine mode of action. PK1 enhanced the net paracellular transport (measured by electrical resistance and Mannitol transport) in LEC but not in BAEC or BCEC. Collectively, these findings indicate that PKs serve as mitogens and survival factors for microvascular (LEC) and macrovascular (BAEC) EC. However, the distinct expression and function of PK receptors suggest different physiological roles for these receptors in various EC types.

Animals↗
PubMed2001

Endothelial function of the popliteal artery in patients with coronary artery disease.

Coronary artery disease (CAD) is associated more closely with atherosclerosis in the popliteal than in the brachial artery. This case-control study aimed at clarifying whether endothelial dysfunction of patients with CAD can be detected non-invasively in the popliteal artery by means of ischemia-induced flow-mediated dilation (FMD) and cold pressor reaction (CPR), and how it compares with the brachial artery. We further investigated a new mode of evaluation of the CPR. Eleven cases with CAD were compared with 16 matched healthy controls. Popliteal and brachial arterial diameter was monitored by ultrasound for 20 min following ischemia and cold pressor. For CPR, the difference between maximum and minimum diameter was defined as maximum vasomotion. In the popliteal artery, maximum vasomotion and FMD were significantly smaller in cases than in controls, the difference being more pronounced than in the brachial artery, where only maximum vasomotion was significantly smaller. After exclusion of current smokers, only the difference in maximum vasomotion of both arteries remained significant. We conclude that maximum vasomotion may be more sensitive for detection of endothelial dysfunction than FMD. Endothelial dysfunction in patients with CAD is more pronounced in the popliteal artery than in the brachial artery.

Adult↗
PubMed2004

The effect of aprotinin on hypoxia-reoxygenation-induced changes in neutrophil and endothelial function.

BACKGROUND AND OBJECTIVE: An acute inflammatory response associated with cerebral ischaemia-reperfusion contributes to the development of brain injury. Aprotinin has potential, though unexplained, neuroprotective effects in patients undergoing cardiac surgery. METHODS: Human neutrophil CD11 b/CD18, endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression and endothelial interleukin (IL)-1beta supernatant concentrations in response to in vitro hypoxia-reoxygenation was studied in the presence or absence of aprotinin (1600 KIU mL(-1)). Adhesion molecule expression was quantified using flow cytometry and IL-1beta concentrations by enzyme-linked immunosorbent assay. Data were analysed using ANOVA and post hoc Student-Newman-Keuls test as appropriate. RESULTS: Exposure to 60-min hypoxia increased neutrophil CD11b expression compared to normoxia (170+/-46% vs. 91+/-27%, P = 0.001) (percent intensity of fluorescence compared to time 0) (n = 8). Hypoxia (60 min) produced greater upregulation of CD11b expression in controls compared to aprotinin-treated neutrophils [(170+/-46% vs. 129+/-40%) (P = 0.04)] (n = 8). Hypoxia-reoxygenation increased endothelial cell ICAM-1 expression (155+/-3.7 vs. 43+/-21 mean channel fluorescence, P = 0.0003) and IL-1beta supernatant concentrations compared to normoxia (3.4+/-0.4 vs. 2.6+/-0.2, P = 0.02) (n = 3). Hypoxia-reoxygenation produced greater upregulation of ICAM- 1 expression [(155+/-3.3 vs. 116+/-0.7) (P = 0.001)] and IL-1beta supernatant concentrations [(3.4+/-0.3 vs. 2.6+/-0.1) (P = 0.01)] in controls compared to aprotinin-treated endothelial cell preparation (n = 3). CONCLUSIONS: Hypoxia-reoxygenation-induced upregulation of neutrophil CD11b, endothelial cell ICAM-1 expression and IL-1beta concentrations is decreased by aprotinin at clinically relevant concentrations.

Analysis of Variance↗
PubMed2002

Endothelial function and oxidative stress in renovascular hypertension.

BACKGROUND: It has been reported that renovascular hypertension activates the renin-angiotensin system, leading to an increase in oxidative stress. We sought to determine whether renal-artery angioplasty improves endothelial dysfunction in patients with renovascular hypertension through a reduction in oxidative stress. METHODS: We evaluated the response of forearm blood flow to acetylcholine, an endothelium-dependent vasodilator, and isosorbide dinitrate, an endothelium-independent vasodilator, before and after renal-artery angioplasty in 15 subjects with renovascular hypertension and 15 controls without hypertension who were matched for age and sex. Forearm blood flow was measured with the use of a mercury-filled Silastic strain-gauge plethysmograph. RESULTS: The forearm blood flow in response to acetylcholine was less in subjects with renovascular hypertension than in controls, although the forearm blood flow in response to isosorbide dinitrate was similar in the two groups. Angioplasty decreased systolic and diastolic blood pressures, forearm vascular resistance, and urinary excretion of 8-hydroxy-2'-deoxyguanosine and serum malondialdehyde-modified low-density lipoprotein (LDL), indexes of oxidative stress. After angioplasty, the mean (+/-SD) forearm blood flow in response to acetylcholine was increased in the patients with renovascular hypertension (19.3+/-6.8 vs. 29.6+/-7.1 ml per minute per 100 ml, P=0.002). The increase in the maximal forearm blood flow in response to acetylcholine correlated significantly with the decrease in urinary excretion of 8-hydroxy-2'-deoxyguanosine (r=-0.51, P=0.004) and serum malondialdehyde-modified LDL (r=-0.39, P=0.02). Coinfusion of ascorbic acid (vitamin C) augmented the response of forearm blood flow to acetylcholine before angioplasty (P<0.001) but not after angioplasty. CONCLUSIONS: These findings suggest that excessive oxidative stress is involved, at least in part, in impaired endothelium-dependent vasodilatation in patients with renovascular hypertension.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2004

Race-specific differences in endothelial function: predisposition of African Americans to vascular diseases.

BACKGROUND: The prevalence of the endothelium-impaired function disorders, such as hypertension and diabetes mellitus, and the severity of their complications are considerably greater in blacks than whites. Evidence has accumulated that superoxide (O2-) production and its interaction with nitric oxide (NO), yielding the strong oxidant peroxynitrite (ONOO-), play central roles in vascular pathophysiology. We hypothesized that the differences in endothelial NO/O2-/ONOO- metabolism may highlight the potential predisposition to endothelial dysfunction and cardiovascular complications prevalent in blacks. METHODS AND RESULTS: Highly sensitive tandem electrochemical NO/O2-/ONOO- nanosensors were positioned in single human umbilical vein endothelial cells (HUVECs) isolated from blacks and whites, and the kinetics of NO/O2-/ONOO- release were recorded in vitro. HUVECs were also analyzed by Western immunoblotting and enzyme activity assays for NAD(P)H-oxidase and endothelial NO synthase (eNOS). Compared with whites, HUVECs from blacks elicited reduced release of bioactive NO with an accompanying increase in the release of both O2- and ONOO-. The greater potency of NO production because of eNOS upregulation in HUVECs from blacks is associated with a decrease in the NO bioavailability. This is due to increased NO degradation by excess O2- produced primarily by 2 enzymatic sources: NAD(P)H-oxidase and uncoupled eNOS. CONCLUSIONS: Compared with whites, the steady-state NO/O2-/ONOO- balance in endothelial cells from blacks is kept closer to the redox states characteristic for the endothelium-impaired function disorders. This may explain the differences in racial predisposition to the endothelium dysfunction during ongoing vascular disturbances with the hallmark of enhanced NO inactivation within the endothelium by oxidative stress.

Acetophenones↗
PubMed1989

Cardiac ischemia and endothelial function in the isolated rabbit heart.

Truly effective prevention of reperfusion myocardial damage is precluded in part by a lack of understanding of the earliest events which accompany ischemia. The purpose of this study was to assess the coronary endothelial response to two forms of ischemic injury in an isolated crystalloid perfused rabbit heart. Global cardiac ischemia, confirmed by NADH fluorescence photography, was induced either by mechanically reducing coronary flow by 90% (MRCF, N = 11) or by an infusion of N-formyl-methionyl-leucyl-phenylalanine (fMLP, N = 11), a known stimulus for leukotriene synthesis and coronary vasospasm. Compared with control, MRCF resulted in an increase in effluent concentrations of both prostacyclin (152 +/- 22 pg/ml vs 951 +/- 214 pg/ml, P less than 0.05) and plasminogen activator (0.8 +/- .3 IU/ml vs 1.4 +/- 0.5, P less than 0.05) but no detectable increase in effluent thromboxane B2 or leukotriene C4 concentrations. fMLP infusion resulted in an immediate reduction in coronary flow coincident with diffuse myocardial ischemia. In contrast to MRCF, however, fMLP-induced ischemia resulted in a significant but smaller increase in effluent prostacyclin concentration (210 +/- 47 pg/ml vs 606 +/- .55 pg/ml, P = 0.05) and a marked increase in both thromboxane B2 (less than or equal to 33 +/- 4 pg/ml vs 1141 +/- 375 pg/ml, P less than 0.05) and leukotriene C4 (less than 0.25 ng/ml vs 3.3 +/- 1.2 ng/ml, P less than 0.05) concentrations. Additionally, fMLP caused a reduction in effluent plasminogen activator activity (0.5 +/- 0.1 IU/ml vs 0.39 +/- 0.1 IU/ml, N = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed2006

Trans fatty acids - effects on systemic inflammation and endothelial function.

Consumption of trans fatty acids (TFA) predicts higher risk of coronary heart disease, sudden death, and possibly diabetes mellitus. These associations are greater than would be predicted by effects of TFA on serum lipoproteins alone. Systemic inflammation and endothelial dysfunction may be involved in the pathogenesis of atherosclerosis, acute coronary syndromes, sudden death, insulin resistance, dyslipidemia, and heart failure. Evidence from both observational and experimental studies indicates that TFA are pro-inflammatory. Limited evidence suggests that pro-inflammatory effects may be stronger for trans isomers of linoleic acid (trans-C18:2) and oleic acid (trans-C18:1), rather than of palmitoleic acid (trans-C16:1), but further study of potential isomer-specific effects is needed. TFA also appear to induce endothelial dysfunction. The mechanisms underlying these effects are not well-established, but may involve TFA incorporation into endothelial cell, monocyte/macrophage, or adipocyte cell membranes (affecting membrane signaling pathway relating to inflammation) or ligand-dependent effects on peroxisome proliferator-activated receptor (PPAR) or retinoid X receptor (RXR) pathways. Activation of inflammatory responses and endothelial dysfunction may represent important mediating pathways between TFA consumption and risk of coronary heart disease, sudden death, and diabetes. Further study is indicated to define these effects of TFA and the implications of such effects for cardiovascular health.

Atherosclerosis↗
PubMed2004

Endothelial function and postprandial lipemia.

It is widely recognised that post-prandial lipoproteins play a role in the development of atherosclerosis, but the mechanisms underlying this role are unclear. An attractive working hypothesis is that the pathogenetic link is endothelial dysfunction. The available data seem to corroborate this theory and recognise triggering by oxidative stress, but some of the evidence is still contradictory.

Animals↗
PubMed2006

Diabetic erectile dysfunction--an indicator of generalised endothelial function per se?

Erectile dysfunction (ED) affects up to 70% of men with diabetes. However, the pathophysiology of ED in diabetes remains uncertain with both neuronal and vascular factors cited. We examined whether ED is an indicator of generalized endothelial dysfunction. A unique group of diabetic patients free from established conventional cardiac risk factors were investigated. Forearm bloodflow responses to nitroprusside and acetylcholine on 11 diabetic men with ED and 11 potent diabetic men were measured by venous plethysmography. Patient characteristics between the impotent and potent patients were similar except for Hba1c which was higher in the group with ED (8.35% vs. 7.03%: p = 0.003). Both groups showed increases in FBF to incremental infusions of nitroprusside and acetylcholine but the area under curve (AUC) were similar in the ED and the non-ED groups (p = 0.16 and p = 0.17, respectively). We demonstrated that ED in patients with type 2 diabetes is not associated with additional generalized endothelial dysfunction.

Area Under Curve↗
PubMed2003

Differential effects of selective cyclooxygenase-2 inhibitors on endothelial function in salt-induced hypertension.

BACKGROUND: In view of the ongoing controversy about potential differences in cardiovascular safety of selective cyclooxygenase (COX)-2 inhibitors (coxibs), we compared the effects of 2 different coxibs and a traditional NSAID on endothelial dysfunction, a well-established surrogate of cardiovascular disease, in salt-induced hypertension. METHODS AND RESULTS: Salt-sensitive (DS) and salt-resistant (DR) Dahl rats were fed a high-sodium diet (4% NaCl) for 56 days. From days 35 to 56, diclofenac (6 mg x kg(-1) x d(-1); DS-diclofenac), rofecoxib (2 mg x kg(-1) x d(-1); DS-rofecoxib), celecoxib (25 mg x kg(-1) x d(-1); DS-celecoxib) or placebo (DS-placebo) was added to the chow. Blood pressure increased with sodium diet in the DS groups, which was more pronounced after diclofenac and rofecoxib treatment (P<0.005 versus DS-placebo) but was slightly decreased by celecoxib (P<0.001 versus DS-placebo). Sodium diet markedly reduced NO-mediated endothelium-dependent relaxations to acetylcholine (10-10-10-5 mol/L) in aortic rings of untreated hypertensive rats (P<0.005 versus DR-placebo). Relaxation to acetylcholine improved after celecoxib (P<0.005 versus DS-placebo and DS-rofecoxib) but remained unchanged after rofecoxib and diclofenac treatment. Vasoconstriction after nitric oxide synthase inhibition, indicating basal NO release, with N(omega)-nitro-L-arginine methyl ester (10-4 mol/L) was blunted in DS rats (P<0.05 versus DR-placebo), normalized by celecoxib, but not affected by rofecoxib or diclofenac. Indicators of oxidative stress, 8-isoprostane levels, were elevated in untreated DS rats on 4% NaCl (6.55+/-0.58 versus 3.65+/-1.05 ng/mL, P<0.05) and normalized by celecoxib only (4.29+/-0.58 ng/mL). CONCLUSIONS: These data show that celecoxib but not rofecoxib or diclofenac improves endothelial dysfunction and reduces oxidative stress, thus pointing to differential effects of coxibs in salt-induced hypertension.

Acetylcholine↗
PubMedDate not supplied

Smoking and endothelial function.

The arterial endothelium is a vital homeostatic cell layer responsible for a variety of functions such as thromboresistance, control of vessel tone, and vessel growth. Recent evidence has indicated that both active and passive cigarette smoking are associated with dysfunction of normal endothelial physiology, in a dose dependent and potentially reversible way. Endothelial abnormalities may predispose to the atherogenic and thrombotic problems associated with cigarette smoking.

Coronary Artery Disease↗
PubMed2004

Mechanisms of soluble beta-amyloid impairment of endothelial function.

Alzheimer's disease (AD) has been recently associated with vascular risk factors. beta-amyloid peptides (AbetaP), the main component of senile plaques typical of AD, circulate in soluble globular form in bloodstream. Interestingly, AbetaP is able to induce endothelial dysfunction, and this effect may represent the link between vascular and neuronal pathophysiological factors involved in AD. We aimed to clarify the molecular mechanisms underlying globular AbetaP-induced vascular toxicity. Using several methodological approaches, we have observed that in vascular tissues globular AbetaP is unable to induce oxidative stress, one of the mechanisms hypothesized involved in beta-amyloid toxicity. More important, we have demonstrated that globular AbetaP is able to localize on vascular endothelium, where it inhibits eNOS enzymatic activity. In particular, AbetaP enhances eNOS phosphorylation on threonine 495 and serine 116 and reduces acetylcholine-induced phosphorylation on serine 1177. Such an effect depends on a PKC signaling pathway, as suggested by its phosphorylation on serine 660. In fact, selective inhibition of the calcium-dependent group of PKC is able to rescue beta-amyloid-induced alteration of eNOS phosphorylation, NO production, and endothelial vasorelaxation. The activation of these Ca(2+)-dependent pathways is probably due to the ability of AbetaP to evoke Ca(2+) leakage from inositol 1,4,5-triphosphate receptors on endoplasmic reticulum. Our data demonstrate that globular AbetaP-induced endothelial NO dysfunction can be attributed to an alteration of intracellular Ca(2+) homeostasis, which could lead to the activation of calcium-dependent group of PKC with a consequent change of the eNOS phosphorylation pattern. These mechanisms could contribute to shed further light on the toxic effect of beta-amyloid in vascular tissues.

Alzheimer Disease↗
PubMed1994

Constrictor and dilator responses to intracoronary acetylcholine in adjacent segments of the same coronary artery in patients with coronary artery disease. Endothelial function revisited.

BACKGROUND: In patients with angiographically detectable atherosclerosis or in those with risk factors for coronary artery disease, intracoronary acetylcholine causes coronary constriction instead of endothelium-derived relaxing factor-mediated dilation. Therefore, it has been hypothesized that diffuse endothelial dysfunction precedes development of coronary atherosclerosis. We tested this hypothesis in a systematic investigation of the effects of ascending doses of acetylcholine on the diameters of nonstenotic segments of the left coronary artery in patients with advanced atherosclerosis and coronary risk factors. METHODS AND RESULTS: Effects of intracoronary infusion of acetylcholine (10(-6) to 10(-4) mol/L) on diameters of proximal, middle, and distal nonstenotic segments of the left coronary artery were studied in 28 consecutive patients with chronic stable angina, positive exercise tests, and angiographic evidence of obstructive atherosclerosis (> or = 50% reduction in lumen diameter in at least one vessel). Two patterns of response to the maximal acetylcholine dose (10(-4) mol/L) were observed. In 21 patients (group 1), only constriction was observed in all left anterior descending and circumflex artery segments studied (16 +/- 3%, 19 +/- 4%, and 23 +/- 4%, respectively; P < .01 compared with control). In 7 other patients (group 2), both constriction and dilation were observed in adjacent segments of the same vessel; maximal acetylcholine dose caused constriction in 14 left anterior descending artery segments from a control diameter of 1.94 +/- 0.19 to 1.33 +/- 0.26 mm (37% reduction, P < .01) and dilation in 16 other segments from 1.63 +/- 0.22 to 1.93 +/- 0.21 mm (25% increase, P < .01). In the circumflex artery, this dose caused constriction in 16 segments from a control diameter of 1.88 +/- 0.14 to 1.33 +/- 0.17 mm (31% reduction, P < .01) and dilation in 12 segments from 1.37 +/- 0.12 to 1.71 +/- 0.09 mm (34% increase, P < .01). CONCLUSIONS: In 25% of patients studied with advanced angiographic coronary atherosclerosis and coronary risk factors, coronary segments with acetylcholine-inducible dilatation are present. In these patients, the endothelium is not diffusely dysfunctional as currently believed but rather shows marked segmental heterogeneity in the response to acetylcholine reflecting degrees of endothelial dysfunction.

Acetylcholine↗
PubMed2005

Oxidized-LDL levels are changed during short-term serum glucose variations and lowered with statin treatment in early Type 2 diabetes: a study of endothelial function and microalbuminuria.

AIMS: To investigate the role of HMG-CoA reductase inhibitor (statin) treatment during serum glucose variations on plasma oxidized LDL (ox-LDL) levels in obese patients with early Type 2 diabetes mellitus (T2D) and its relationship to endothelial biomarkers. METHODS: In a double-blind, randomized crossover study, 15 obese diet-treated T2D patients received cerivastatin (0.4 mg/day) or placebo for 3 months. Circulating ox-LDL levels were measured fasting and during a euglycaemic-hyperinsulinaemic clamp (approximately 5.5 mmol/l; EHC) and a hyperglycemic clamp (approximately 20 mmol/l; HC). An endothelium-dependent flow-mediated dilation (FMD) study was carried out and urinary albumin excretion (UAE) was measured at rest and during EHC. S-ICAM, s-VCAM and basal prothrombotic factors were also measured. RESULTS: During cerivastatin treatment, basal circulating ox-LDL levels decreased by 48% (P<0.001) compared with placebo. Serum ox-LDL levels decreased during EHC and remained unchanged during HC compared with the fasting state; with cerivastatin treatment these levels were lower compared with placebo both in the fasting state and during the clamp studies. FMD was higher with cerivastatin than with placebo (P<0.001) and the increments in FMD correlated with decrements in serum ox-LDL levels (r=0.78, P=0.001). Microalbuminuria increased during EHC but this was blunted during cerivastatin therapy compared with placebo (P<0.05). Basal sICAM-1 and sVCAM-1 levels decreased (P<0.01 and P<0.05, respectively). CONCLUSIONS: In early obese Type 2 diabetic patients, serum ox-LDL levels are influenced by short-term serum glucose variations and lowered with cerivastatin therapy. During cerivastatin treatment, improved flow-mediated endothelium-dependent dilation was associated with decrements in circulating ox-LDL levels and the hyperinsulinaemia-induced urinary albumin excretion was blunted.

Adult↗
PubMed1986

Alterations of presynaptic and endothelial functions in SHR: effects of adenosine.

The effects of adenosine on stimulation-evoked 3H-efflux from perfused mesenteric arteries pretreated with 3H-norepinephrine and on norepinephrine-induced contractile responses of the thoracic aorta before and after mechanical removal of endothelial cells were examined in spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). Adenosine inhibited the stimulation-evoked 3H-efflux; this inhibitory effect was smaller in young and adult SHR than age-matched WKY. Mechanical removal of endothelial cells rendered the SHR aorta much less responsive to adenosine, while in the WKY aorta endothelial removal had no influence on the relaxation response to adenosine. These results support the hypothesis that pre-synaptic factors are contributory whereas endothelial factors are compensatory to hypertension in SHR.

Adenosine↗
PubMed2003

Effect of genistein and daidzein on platelet aggregation and monocyte and endothelial function.

There has been much recent interest in the cardiovascular benefits of dietary isoflavones. The aim of the present in vitro studies was to investigate potential anti-thrombogenic and anti-atherogenic effects of the isoflavones genistein and daidzein in platelets, macrophages and endothelial cells. Pre-treatment with either isoflavone inhibited collagen-induced platelet aggregation in a dose-dependent manner. In a macrophage cell line (RAW 264.7) activated with interferon gamma plus lipopolysaccharide, both isoflavones were found to inhibit NO production and tumour necrosis factor alpha (TNF-alpha) secretion dose-dependently, but they did not affect mRNA levels for inducible nitric oxide synthase and cyclo-oxygenase-2. Both isoflavones also dose-dependently decreased monocyte chemoattractant protein-1 secretion induced by TNF-alpha in human umbilical vein endothelial cells. Compared with daidzein, genistein exerted greater inhibitory effects for all parameters studied. The present data contributes to our knowledge on the molecular mechanisms by which isoflavones may protect against coronary artery disease. Further studies are required to determine whether the effects of isoflavones observed in the current in vitro studies are relevant to the aetiology of coronary artery disease in vivo.

Analysis of Variance↗