Plasma Markers Of Endothelial Activation Research Articles

Impact of DPP-4 inhibition on acute and chronic endothelial function in humans with type 2 diabetes on background metformin therapy.

NCT01859793.

Endothelial Activation and Blood-Brain Barrier Injury as Risk Factors for Delirium in Critically Ill Patients.

During critical illness, impaired endothelial vascular reactivity predicts prolonged acute brain dysfunction, but relationships between endothelial activation, blood-brain barrier/neurological injury, and acute brain dysfunction, including delirium, remain unexamined. We tested the hypothesis that elevated plasma markers of endothelial activation and blood-brain barrier/neurological injury are associated with delirium duration during critical illness. Prospective cohort study. Medical and surgical ICUs in an academic medical center. Adults in acute respiratory failure and/or shock. None. We enrolled subjects within 72 hours of organ failure diagnosis in the ICU. We measured plasma concentrations of plasminogen activator inhibitor-1, E-selectin, and angiopoietin-2 as markers of endothelial activation and S100B as a marker of blood-brain barrier/neurological injury in blood collected at enrollment. We assessed patients for delirium and coma twice daily after enrollment using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale. Among 134 patients with a median (interquartile) age of 57 years (46-66 yr) and Acute Physiology and Chronic Health Evaluation II of 26 (19-31), delirium occurred in 94 patients (70%) with a median duration of 2 days (0-4 d). Higher plasminogen activator inhibitor-1 (p = 0.002), E-selectin (p = 0.02), and S100B (p < 0.001) concentrations were associated with fewer delirium/coma-free days after adjusting for age, Charlson comorbidity index, modified Sequential Organ Failure Assessment score, and severe sepsis. Similarly, higher plasminogen activator inhibitor-1 (p = 0.007) and S100B (p = 0.01) concentrations were associated with longer delirium duration in survivors. Adjusting for S100B did not alter plasminogen activator inhibitor-1 and E-selectin associations with delirium, suggesting that these associations were not mediated by blood-brain barrier/neurological injury. Elevated plasma markers of endothelial activation and blood-brain barrier/neurological injury during critical illness are associated with prolonged delirium after biomarker measurement. Future research is needed to determine whether these processes have pathophysiologic roles in delirium and whether therapies targeted at the endothelium or blood-brain barrier can prevent and/or treat delirium during critical illness.

Left Ventricular Fibrosis in Atrial Fibrillation

Excessive atrial fibrosis is involved in the pathogenesis of atrial fibrillation (AF), but little is known of left ventricular (LV) fibrotic status in patients with AF. In the present study, we investigated the presence of abnormal LV fibrosis in AF, its effect on cardiac function, a possible association with arterial stiffness (i.e., systemic cardiovascular fibrosis), and the parameters of endothelial activation, dysfunction, and damage. We also studied whether LV fibrosis could be linked to the future risk of AF onset. In a cross-sectional study, the severity of LV fibrosis was assessed by echocardiographic acoustic densitometry in patients with permanent AF (n = 49), patients with paroxysmal AF (n = 44), AF-free "disease controls" (n = 42) and "healthy controls" (n = 48). Arterial stiffness (pulse wave velocity), plasma markers of endothelial activation (E-selectin), endothelial damage/dysfunction (von Willebrand factors), and microvascular endothelial function (laser Doppler flowmetry) were quantified. In a longitudinal study, 93 patients with pacemakers (22 with AF) were followed up for ≥1 year to assess the predictive value of LV fibrosis for the development of new-onset AF. More severe LV fibrosis was present in both paroxysmal and permanent AF than in the AF-free controls (p <0.001), with more LV fibrosis in permanent than in paroxysmal AF (p = 0.002). The severity of LV fibrosis in AF wais independently associated with diastolic dysfunction (p = 0.03), but not with LV contractility, arterial stiffness, or endothelial damage/dysfunction. In conclusion, LV fibrosis might contribute to LV diastolic dysfunction and the high prevalence of heart failure with preserved ejection fraction in subjects with AF.

NFκB in the development of endothelial activation and damage in uremia: an in vitro approach.

Impaired hemostasis coexists with accelerated atherosclerosis in patients with chronic kidney disease (CKD). The elevated frequency of atherothrombotic events has been associated with endothelial dysfunction. The relative contribution of the uremic state and the impact of the renal replacement therapies have been often disregarded. Plasma markers of endothelial activation and damage were evaluated in three groups of patients with CKD: under conservative treatment (predialysis), on hemodialysis, and on peritoneal dialysis. Activation of p38 MAPK and the transcription factor NFκB was assessed in endothelial cell (EC) cultures exposed to pooled sera from each group of patients. Most of the markers evaluated (VCAM-1, ICAM-1, VWF, circulating endothelial cells) were significantly higher in CDK patients than in controls, being significantly more increased in the group of peritoneal dialysis patients. These results correlated with the activation of both p38 MAPK and NFκB in EC cells exposed to the same sera samples, and also to the peritoneal dialysis fluids. Hemodialysis did not further contribute to the endothelial damage induced by the uremic state observed in predialysis patients, probably due to the improved biocompatibility of the hemodialysis technique in recent years, resulting in lower cellular activation. However, peritoneal dialysis seemed to exert a significant proinflammatory effect on the endothelium that could be related to the high glucose concentrations and glucose degradation products present in the dialysis fluid. Although peritoneal dialysis has been traditionally considered a more physiological technique, our results raise some doubts with respect to inflammation and EC damage.

Vascular inflammation in cerebral small vessel disease

Cerebral small vessel disease (CSVD) is considered to be caused by an increased permeability of the blood-brain barrier and results in enlargement of Virchow Robin spaces (VRs), white matter lesions, brain microbleeds, and lacunar infarcts. The increased permeability of the blood-brain barrier may relate to endothelial cell activation and activated monocytes/macrophages. Therefore, we hypothesized that plasma markers of endothelial activation (adhesion molecules) and monocyte/macrophage activation (neopterin) relate to CSVD manifestations. In 163 first-ever lacunar stroke patients and 183 essential hypertensive patients, we assessed CSVD manifestations on brain magnetic resonance imaging (MRI) and levels of C-reactive protein (CRP), neopterin, as well as circulating soluble adhesion molecules (sICAM-1, sVCAM-1, sE-selectin, sP-selectin). Neopterin, sICAM-1 and sVCAM-1 levels were higher in patients with extensive CSVD manifestations than in those without (p < 0.01). Neopterin levels independently related to higher numbers of enlarged Virchow Robin spaces (p < 0.001). An inflammatory process with activated monocytes/macrophages may play a role in the increased permeability of the blood brain barrier in patients with CSVD.

Circulating adenosine increases during human experimental endotoxemia but blockade of its receptor does not influence the immune response and subsequent organ injury

IntroductionPreclinical studies have shown that the endogenous nucleoside adenosine prevents excessive tissue injury during systemic inflammation. We aimed to study whether endogenous adenosine also limits tissue injury in a human in vivo model of systemic inflammation. In addition, we studied whether subjects with the common 34C > T nonsense variant (rs17602729) of adenosine monophosphate deaminase (AMPD1), which predicts increased adenosine formation, have less inflammation-induced injury.MethodsIn a randomized double-blinded design, healthy male volunteers received 2 ng/kg E. Coli LPS intravenously with (n = 10) or without (n = 10) pretreatment with the adenosine receptor antagonist caffeine (4 mg/kg body weight). In addition, lipopolysaccharide (LPS) was administered to 10 subjects heterozygous for the AMPD1 34C > T variant.ResultsThe increase in adenosine levels tended to be more pronounced in the subjects heterozygous for the AMPD1 34C > T variant (71 ± 22%, P=0.04), compared to placebo- (59 ± 29%, P=0.012) and caffeine-treated (53 ± 47%, P=0.29) subjects, but this difference between groups did not reach statistical significance. Also the LPS-induced increase in circulating cytokines was similar in the LPS-placebo, LPS-caffeine and LPS-AMPD1-groups. Endotoxemia resulted in an increase in circulating plasma markers of endothelial activation [intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)], and in subclinical renal injury, measured by increased urinary excretion of tubular injury markers. The LPS-induced increase of these markers did not differ between the three groups.ConclusionsHuman experimental endotoxemia induces an increase in circulating cytokine levels and subclinical endothelial and renal injury. Although the plasma adenosine concentration is elevated during systemic inflammation, co-administration of caffeine or the presence of the 34C > T variant of AMPD1 does not affect the observed subclinical organ damage, suggesting that adenosine does not affect the inflammatory response and subclinical endothelial and renal injury during human experimental endotoxemia.Trial RegistrationClinicalTrials (NCT): NCT00513110.

Relationship of Soluble Adhesion Receptors to Red Cell Apoptosis In SCD.

AbstractAbstract 1654The interaction of sickle red cells (SS RBCs) with endothelium can cause endothelial injury, leading to increased expression of soluble endothelial cell adhesion molecules and plasma markers of endothelial activation and dysfunction. Among such plasma markers, sVCAM-1 levels are increased in SCD and rise further during vaso-occlusive crisis (Duits et al. 1993), and several groups have shown that sVCAM-1 levels are positively related to LDH levels, a marker of hemolysis. Perfusion of endothelial cells with SS RBCs has been shown to increase the expression of the cellular adhesion molecules ICAM-1 and VCAM-1 by endothelial cells (Shiu et al. 2000). Furthermore, sVCAM-1, sICAM-1, and sE-selectin have been independently associated with risk of mortality (Kato et al. 2005). We were interested in determining whether identifiable characteristics of SS RBCs themselves might be associated with the degree to which soluble adhesion molecules are expressed in SCD patient plasma. Therefore, we measured sVCAM-1, sICAM-1, sCD40 ligand (sCD40L) and sP-selectin in SCD patient plasma by ELISA (n=46) and looked at the relationship of these biomarkers of disease activity to SS RBC characteristics. We specifically examined phosphatidylserine exposure (as measured by annexin V binding analyzed by flow cytometry) and the degree of SS RBC adhesion to laminin and endothelial cells, measured in vitro in a graduated height flow chamber. We found that the degree of red cell damage measured by annexin V binding correlated with the level of soluble adhesion receptors sVCAM-1 (p=0.036) and sICAM-1 (p=0.026). However, annexin V binding did not correlate with sCD40L or sP-selectin expression in plasma, and neither annexin V binding nor levels of soluble adhesion molecules correlated with SS RBC adhesion to laminin or endothelial cells in vitro. In addition, the concentrations of sVCAM-1 and sICAM-1 in plasma were strongly correlated with each other (p<0.0001), suggesting that both of these adhesion molecules may be released from activated endothelial cells in SCD patients as a result of the same mechanism involving contact with phosphatidylserine-exposing SS RBCs. These data support the hypothesis that phosphatidylserine exposure on SS RBCs is a critical factor in SS RBC interaction with the endothelium (Setty et al., 2002), including the release of soluble cellular adhesion markers that indicate endothelial activation and/or injury. Disclosures:Telen:GlycoMimetics, Inc.: Consultancy.

Longitudinal Assessment of Maternal Endothelial Function and Markers of Inflammation and Placental Function throughout Pregnancy in Lean and Obese Mothers

Obesity in pregnancy is increasing and is a risk factor for metabolic pathology such as preeclampsia. In the nonpregnant, obesity is associated with dyslipidemia, vascular dysfunction, and low-grade chronic inflammation. Our aim was to measure microvascular endothelial function in lean and obese pregnant women at intervals throughout their pregnancies and at 4 months after delivery. Plasma markers of endothelial function, inflammation, and placental function and their association with microvascular function were also assessed. Women in the 1st trimester of pregnancy were recruited, 30 with a body mass index (BMI) less than 30 kg/m(2) and 30 with a BMI more than or equal to 30 kg/m(2) matched for age, parity, and smoking status. In vivo endothelial-dependent and -independent microvascular function was measured using laser Doppler imaging in the 1st, 2nd, and 3rd trimesters of pregnancy and at 4 months postnatal. Plasma markers of endothelial activation [soluble intercellular cell adhesion molecule-1 (sVCAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF), and plasminogen activator inhibitor (PAI)-1], inflammation (IL-6, TNFalpha, C-reactive protein, and IL-10), and placental function (PAI-1/PAI-2 ratio) were also assessed at each time point. The pattern of improving endothelial function during pregnancy was the same for lean and obese, but endothelial-dependent vasodilation was significantly lower (P < 0.05) in the obese women at each trimester (51, 41, and 39%, respectively). In the postpartum period, the improvement in endothelial-dependent vasodilation persisted in the lean women but declined to near 1st trimester levels in the obese (lean/obese difference, 115%; P < 0.01). There was a small but significant difference in endothelial-independent vasodilation between the two groups, lean response being greater than obese (P = 0.021), and response declined in both groups in the postpartum period. In multivariate analysis, time of sampling had the most impact on endothelial-independent function [18.5% (adjusted sum of squares expressed as a percentage of total means squared), P < 0.001 for sodium nitroprusside response; 9.8%, P < 0.001 for acetylcholine response], and obesity had the most impact on endothelial-dependent microvascular function (1.7%, P = 0.046 for sodium nitroprusside response; 19.3%, P < 0.001 for acetylcholine response). Time of sampling (11.2%, P < 0.001), IL-6 (4.0%, P = 0.002), and IL-10 (2.4%, P = 0.018) were significant independent contributors to variation in endothelial-dependent microvascular function. When obesity was entered into the model, the association with IL-6 and IL-10 was no longer significant, and obesity explained 6.8% (P < 0.001) of the variability in endothelial-dependent microvascular function. In the 1st trimester, obese women had a significantly higher PAI-1/PAI-2 ratio [obese median (interquartile range), 0.87 (0.54-1.21) vs. lean 0.30 (0.21-0.47), P < 0.001), reflecting the lower PAI-2 levels in obese pregnant women. In a multivariate analysis, 1st trimester BMI (7.6%, P = 0.012), IL-10 (8.2%, P < 0.001), and sVCAM-1 (0.73%, P = 0.007) contributed to the 1st trimester PAI-1/PAI-2 ratio. Obese mothers have a lower endothelium-dependent and -independent vasodilation when compared with lean counterparts. There was a higher PAI-1/ PAI-2 ratio in the 1st trimester in obese women, which improved later in pregnancy. Obese pregnancy is associated with chronic preexisting endothelial activation and impairment of endothelial function secondary to increased production of inflammatory T-helper cells-2 cytokines.

Statins and Cerebral Vasomotor Reactivity

See related article, pages 2540-2545. Animal models have shown that cholesterol-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (commonly called statins) may augment absolute cerebral blood flow (CBF) by enhancing nitric oxide synthase (eNOS).1 Statins upregulate type III endothelial eNOS in thrombocytes, decrease platelet activation, and protect from cerebral ischemia in normocholesterolemic mice.2 Statins may also provide additional beneficial effects by upregulating endogenous tissue plasminogen activator and enhancing clot lysis in a mouse model of embolic focal ischemia.3 Statins given 24 hours after experimental ischemia can enhance CBF, angiogenesis, neurogenesis and sinaptogenesis.4 How can these findings be applied in the clinical setting? A meta-analysis of published clinical trials showed that low-density lipoprotein–lowering with statins may decrease the risk of stroke in diabetic or hypertensive patients with normal low-density lipoprotein cholesterol at baseline, and in patients with coronary artery disease, with respectively 48%, 27% and 25% reduction in stroke incidence.5 Does any relationship exist among statins and cerebral vasomotor reactivity? Functional transcranial Doppler (TCD) ultrasonography permits the assessment of cognitively induced CBF velocity changes6 and the evaluation of cerebral vasomotor reactivity.7 TCD can be used to reliably evaluate age-related changes in the physiological response of the human cerebral circulation. A diminished nitric oxide–mediated cerebral vasomotor response may exist in aging subjects and in patients with vascular risk factors.8 Because there are no reliable markers for the functional status of the cerebral small vessels in elderly patients at risk of stroke, TCD studies may be useful. Although some parameters …

Impaired Flow-Mediated Vasodilation, Carotid Artery Intima-Media Thickening, and Elevated Endothelial Plasma Markers in Obese Children: The Impact of Cardiovascular Risk Factors

Childhood obesity contributes to the development of adult obesity and subsequent cardiovascular disease. The present study aimed to assess vascular status (flow-mediated vasodilation [FMD], intima-media thickness [IMT]) and to analyze plasma surrogate endothelial markers (von Willebrand factor [vWf], E-selectin, and thrombomodulin) in obese children as compared with controls. Associations between early morphologic and functional vascular changes, surrogate soluble markers of early atherosclerosis, and the cardiovascular risk profile were determined. We examined 32 obese children versus 20 control subjects. All of the children underwent identical screening, comprehensive risk factor assessment, and measurements of E-selectin, vWf, thrombomodulin, FMD, and IMT. Compared with controls, obese children demonstrated significantly impaired FMD and increased IMT. Concentrations of soluble E-selectin and thrombomodulin were significantly elevated in obese children, whereas vWf showed no significant differences between obese children and controls. FMD, IMT, E-selectin, and thrombomodulin were significantly associated with various risk factors, including the extent of obesity, arterial hypertension, fibrinogen, C-reactive protein, and low physical fitness. The present study documented increased IMT, impaired endothelial function, and elevated plasma markers of endothelial activation and injury in obese children. Morbid obesity, arterial hypertension, subclinical inflammation, and low physical fitness formed a risk profile associated with the risk of early atherosclerosis in these children. Sonographic assessment of vascular status and the estimation of soluble endothelial plasma markers, combined with comprehensive risk factor screening, may form a rationale to identify high-risk children susceptible to early atherosclerotic disease and to monitor vascular changes during follow-up studies and therapeutic measures.

Current Literature: Effect of Antioxidants on the Occurrence of Pre‐eclampsia in Women at Increased Risk: A Randomised Trial

Background: Oxidative stress has been implicated in the pathophysiology of pre‐eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre‐eclampsia. Methods: 283 women were identified as being at increased risk of pre‐eclampsia by abnormal two‐stage uterine‐artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16–22 weeks' gestation. Plasma markers of endothelial activation (plasminogen‐activator inhibitor 1 [PAI‐1]) and placental dysfunction (PAI‐2) were measured every month until delivery. Pre‐eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study. Findings: Supplementation with vitamins C and E was associated with a 21% decrease in the PAI‐1/PAI‐2 ratio during gestation (95% CI 4–35, p = 0.015). In the intention‐to‐treat cohort, pre‐eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17–0.90], p = 0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre‐eclampsia was 0.24 (0.08–0.70, p = 0.002). Interpretation: Supplementation with vitamins C and E may be beneficial in the prevention of pre‐eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre‐eclampsia in low‐risk women and to confirm our results in larger groups of high‐risk women from different populations. (Lancet 354:810–816, 1999)

Effect of Antioxidants on the Occurrence of Pre-Eclampsia in Women at Increased Risk: A Randomised Trial

Summary Background Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia. Methods 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16–22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study. Findings Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4–35, p=0·015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0·39 [0·17–0·90], p=0·02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0·24 (0·08–0·70, p=0·002). Interpretation Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.

Fluvastatin Decreases Soluble Thrombomodulin in Cardiac Transplant Recipients

We conducted a randomized, placebo controlled, double-blind, cross-over study, to assess the effects of a 4-week fluvastatin therapy on plasma markers of endothelial activation or injury in 20 transplanted heart recipients. The levels of thrombomodulin and von Willebrand factor antigen were higher at baseline in cardiac transplant recipients than in age and sex-matched healthy controls. Plasma total cholesterol showed a 21% reduction on fluvastatin therapy (p = 0.0001). Fluvastatin treatment had no significant effect on creatininemia, plasma cyclosporine, PAI-1 antigen, PAI-1 activity, tPA antigen, and Von Willebrand factor. However, fluvastatin produced a significant decrease of plasma thrombomodulin (66.7 ng/ml on placebo versus 58.8 ng/ml on fluvastatin, p <0.001), suggesting a rapid improvement of endothelial injury in these patients.

Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial

Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia. 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study. Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0.24 (0.08-0.70, p=0.002). Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.

Endothelial Activation Response to Oral Micronised Flavonoid Therapy in Patients with Chronic Venous Disease – a Prospective Study

Backgroundendothelial activation is important in the pathogenesis of skin changes due to chronic venous disease (CVD). Purified micronised flavonoid fraction has been used for symptomatic treatment of CVD for a considerable period of time. The exact mode of action of these compounds remains unknown.Aimto study the effects of micronised purified flavonoidic fraction (Daflon® 500 mg, Servier, France) treatment on plasma markers of endothelial activation.Materials and methodstwenty patients with chronic venous disease were treated for 60 days with DAFLON® 500 mg twice daily. Duplex ultrasonography and PPG was used to assess the venous disease. Blood was collected from a foot vein immediately before starting treatment and within 1 week of stopping treatment. Plasma markers of endothelial activation were measured using commercial ELISA kits.Resultsreduction in the level of ICAM-1, 32% (141 ng/ml: 73 ng/ml) and VCAM 29% (1292 ng/ml: 717 ng/ml) was seen. Reduction in plasma lactoferrin (36% decrease, 760 ng/ml: 560 ng/ml) and VW factor occurred in the C4 group only.Conclusionsmicronised purified flavonoidic fraction treatment for 60 days seems to decrease the levels of some plasma markers of endothelial activation. This could ameliorate the dermatological effects of (CVD). This could also explain some of the pharmacological actions of these compounds. Our study demonstrates the feasibility of using soluble endothelial adhesion molecules as markers for treatment.