Anti-endothelial cell autoantibodies and soluble markers of endothelial cell dysfunction in systemic lupus erythematosus.

Objective: To determine if anti-endothelial cell antibodies (AECA) and plasma markers of endothelial cell function are related to disease severity in systemic lupus erythematosus (SLE).

Methods: We measured AECA by human umbilical vein endothelial cell binding, endothelial markers von Willebrand factor, soluble thrombomodulin, and soluble E-selectin by ELISA, and disease severity by SLEDAI and SLICC/ACR in 35 patients with SLE.

Results: Despite high levels of IgG AECA (p = 0.

Interleukin-6, tissue factor and von Willebrand factor in acute decompensated heart failure: relationship to treatment and prognosis.

Arterial thrombotic and thromboembolic complications are increased in congestive heart failure (CHF), and are a particular problem in acute decompensated heart failure, which carries a poor prognosis. As interleukin-6 (IL-6) has been shown to induce the potent procoagulant tissue factor (TF) in experimental models, we hypothesized that the pro-inflammatory IL-6 may be one mechanism contributing to thrombosis in heart failure, mediated via endothelial expression of TF on activated/damaged cells [indicated by plasma von Willebrand factor (vWF)]. Seventy-seven patients (67% men, New York Heart Association class III-IV, 87%) with acute CHF were recruited, and were compared with 53 chronic stable CHF patients in sinus rhythm (66% men, New York Heart Association class III-IV, 2%) and 37 healthy controls (68% men).

Effects of C-reactive protein on the release of von Willebrand factor, E-selectin, thrombomodulin and intercellular adhesion molecule-1 from human umbilical vein endothelial cells.

Increased levels of various plasma molecules, including C-reactive protein (CRP), and endothelial markers von Willebrand factor (vWF), E-selectin, intercellular adhesion molecule-1 (ICAM-1) and thrombomodulin all predict the development and/or progression of cardiovascular disease. As CRP has been shown to upregulate the expression of adhesion molecules on the surface of human umbilical vein endothelial cells (HUVECs) in vitro, we hypothesized that CRP would induce the release of increased levels of the endothelial markers from HUVECs. Accordingly, recombinant human CRP was added to the culture medium of confluent monolayers of HUVECs at physiological to pathological doses of 1-50 microg/ml for 3-48 h.

Relation of thrombogenesis in systemic hypertension to angiogenesis and endothelial damage/dysfunction (a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial [ASCOT]).

Increasing evidence points toward a prothrombotic state in hypertension and atherosclerosis, conditions associated with thrombosis-related complications, such as myocardial infarction and stroke. We hypothesized that this increased risk of thrombogenesis may be related to endothelial damage/dysfunction and abnormal angiogenesis, and thus, an increased risk of future cardiovascular disease. Thrombogenesis, endothelial damage/dysfunction, and angiogenesis can be assessed by measurement of tissue factor (TF), von Willebrand Factor (vWF), flow-mediated dilatation (FMD), and vascular endothelial growth factor (VEGF), respectively.

Interleukin-6, endothelial activation and thrombogenesis in chronic atrial fibrillation.

Background: A prothrombotic or hypercoagulable state has been described in AF, which could increase the risk of thromboembolism. As inflammation has been related to thrombogenesis and endothelial activation, we hypothesised that the prothrombotic state in AF (as assessed by an index of thrombogenesis, prothrombin fragment 1+2 [F1+2]) and endothelial activation (soluble E-selectin (sEsel)) could be related to an index of inflammation (interleukin-6 (IL-6)).

Patients And Methods: We studied 191 consecutive patients (98 male; mean age 72.

A comparison of flow-mediated dilatation and von Willebrand factor as markers of endothelial cell function in health and in hypertension: relationship to cardiovascular risk and effects of treatment: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial.

Loss of adequate endothelial cell function (associated with various cardiovascular syndromes such as hypertension) is most widely quantified by assessing flow-mediated dilatation (FMD) or measuring plasma markers such as von Willebrand factor (vWF). However, the relationship between these two methods is unclear, as is their relationship to 10-year cardiovascular risk (defined by the Framingham equation) and their response to intensive cardiovascular risk factor management. We tested the hypothesis that there is an inverse relationship between vWF and FMD by measuring both in 132 subjects, of whom 89 were hypertensive (mean blood pressure, 167/91 mmHg) and 43 were healthy normotensive (mean blood pressure, 133/80 mmHg).

Neither carvedilol nor bisoprolol in maximally tolerated doses has any specific advantage in lowering chronic heart failure oxidant stress: implications for beta-blocker selection.

We hypothesized that abnormal oxidative stress in chronic heart failure (CHF) could be related to endothelial damage and platelet activation, and that the vasodilating beta-blocker carvedilol would have beneficial effects on these processes compared with a selective non-vasodilating cardioselective beta-blocker, bisoprolol. We therefore assessed the effects of introducing carvedilol and bisoprolol in a prospective manner on indices of oxidative stress [lipid hydroperoxides (LHP)], endothelial damage [von Willebrand factor (vWf)], platelet activation (soluble P-selectin) and coagulation (fibrinogen) and their inter-relationships in stable outpatients with CHF in sinus rhythm. We recruited 46 patients [23 male; age 64 +/- 13 years (mean +/- S.

Post-stroke inflammatory response: effects of stroke evolution and outcome.

Recovery after stroke is often hindered by further neurologic deterioration, which can affect up to 45% of patients. It has been suggested that one of the major causes of this neurologic deterioration may be post-ischemic cerebral inflammation. This review presents the basis of pathophysiologic mechanisms of post-stroke inflammation and discusses possible targets and routes for therapeutic intervention.

Pharmacological modulation of platelet function in hypertension.

Platelets exert a considerable influence on human morbidity and mortality. The rationale for their study in hypertension follows the observation that the major consequences of hypertension are stroke and myocardial infarction. However, the etiology of these consequences in hypertension is, paradoxically, not hemorrhagic (as might be expected from the effects of high blood pressure), but occlusive, with thrombus being the culprit lesion.

Enalapril does not alter adhesion molecule levels in human endotoxemia.

The angiotensin-converting enzyme inhibitor (ACE-I) enalapril has been shown to lower elevated levels of circulating adhesion molecules (cAM) in critically ill patients. To delineate the mechanisms of this possibly beneficial effect of enalapril, we studied the acute effects of enalapril in a well-defined model of endotoxin-triggered, cytokine-mediated cAM up-regulation. In a randomized, controlled trial, 30 healthy male volunteers received 2 ng/kg lipopolysaccharide (LPS) after pretreatment with placebo or 20 mg/day enalapril for 5 days or with a single dose of 20 mg of enalapril 2 h before LPS infusion.

Platelet activation and endothelial cell dysfunction in sickle cell disease is unrelated to reduced antioxidant capacity.

Possible pathogenetic processes in sickle cell disease include antioxidants, endothelial and platelet changes, and hypercoagulability. Hypothesizing relationships between these processes, we recruited 47 young adult patients (mean age 19 years) with homozygous sickle cell disease and 40 age-, race- and sex-matched healthy controls and measured plasma markers representative of these processes. We found raised plasma von Willebrand factor (P = 0.

Soluble adhesion molecules in clinical ischaemic injury.

Background: Neutrophil adhesion is a prerequisite for ischaemic injury. In vitro research has shown that soluble adhesion molecules have an inhibitory effect on neutrophil binding

Aims: To determine whether the circulating forms of adhesion molecules are consumed during skeletal muscle ischaemic injury in man.

Methods: The response of the circulating forms of adhesion molecules ICAM-1 (intercellular adhesion molecule-1) and L-selectin to ischaemia and reperfusion was investigated in 23 patients during surgery involving aortic cross-clamping and in 20 volunteers with tourniquet-induced forearm ischaemia.

Anti-oxidative properties of beta-blockers and angiotensin-converting enzyme inhibitors in congestive heart failure.

Background: Chronic elevation of plasma catecholamines and sympathetic stimulation in chronic heart failure (CHF) leads to increased production of free radicals, and so possibly to endothelial damage/dysfunction and atheroma formation. Abnormal oxidative stress may therefore be related to some of the high mortality and morbidity in CHF. The objective of the present prospective open study was to compare the effects of beta-blockers and ACE inhibitors in relation to oxidative stress and endothelial damage in CHF.

Low-density lipoprotein subfractions and cardiovascular risk in hypertension: relationship to endothelial dysfunction and effects of treatment.

Although hypertensive patients are at particular risk of vascular complications, the possible contribution of an atherogenic lipoprotein profile and endothelial dysfunction to this risk is unclear. We investigated this by measuring LDL subfractions and flow-mediated dilation (FMD) (reflecting endothelial dysfunction) in a cohort of high-risk hypertensive patients. We studied 84 hypertensive patients (74 men; mean age, 64 years; SD 8).

Physical activity in relation to indices of endothelial function and angiogenesis factors in hypertension: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

Background: Hypertension is an important risk factor for cardiovascular disease. The latest guidelines recommend regular physical exercise as initial step or adjunct in the treatment of hypertension. We investigated the association between physical activity and the degree of hypertension, as well as the relation to indices of endothelial damage/dysfunction and angiogenesis.