Decreased number of circulating CD34+KDR+ cells in asymptomatic subjects with preclinical atherosclerosis.

OBJECTIVES: To assess whether circulating endothelial progenitor cells (CEPCs) can be considered as a cardiovascular risk marker before event has occurred, that is less firmly established than in clinically overt atherosclerosis. METHODS: Number of CD34+KDR+ cell number per ml blood was measured by flow cytometry in 84 untreated subjects without cardiovascular disease. Atherosclerotic plaque was detected by ultrasound in carotid, abdominal aortic and femoral sites and the number of sites affected by plaque among these three sites was counted as 0, 1, 2 or 3. Additionally, intima-media thickness (IMT) was measured by computerized ultrasound imaging of both common carotid segments. RESULTS: CD34+KDR+ cell number decreased by 48, 29 or 30% in the presence of carotid, aortic or femoral plaque (p<0.001, 0.05, 0.05, respectively) as compared to the absence of plaque and by 70% in the presence of three sites affected with plaque as compared with 0 site with plaque (p<0.01) but did not change with increasing IMT tertiles. Adjustment for Framingham risk score, that was also associated with decreased CD34+KDR+ cell number (p<0.001), made CD34+KDR+ cell number associations with plaque insignificant, except at the carotid site (p<0.01). CONCLUSIONS: Reduced CEPC number may participate to preclinical stage of atherosclerosis and provide additional information to traditional risk factors as regards global risk assessment.

Plasma cGMP and large artery remodeling in asymptomatic men.

cGMP regulates vascular smooth muscle tone and arterial wall response to proliferative signals. We determined plasma cGMP and carotid artery intima-media thickness (IMT) and diameter in 84 asymptomatic men submitted to investigation of their cardiovascular risk profiles. Plasma cGMP was positively associated with IMT (P<0.01) and diameter (P<0.05), independently of coexisting risk factors. These associations were reinforced in the subgroup of subjects with high-sensitivity C-reactive protein level or multiple atherosclerotic plaques. A positive relationship existed between diameter and IMT (P<0.01) and disappeared after cGMP adjustment. This suggests a link between cGMP pathway and arterial wall geometry that is revealed by vascular injury conditions and may participate in early large artery remodeling.

Therapeutic immunoglobulin reduces Ca2+ mobilization and von Willebrand factor secretion, and increases nitric oxide release in human endothelial cells.

Intravenous gamma-immunoglobulin (i.v.Ig) is commonly used in the treatment of autoimmune and inflammatory vascular disorders to prevent thrombotic complications. The mechanism of action of i.v.Ig is, however, not yet elucidated. In view of this, we investigated the ability of i.v.Ig to modulate i) Ca(2+) signals of fura-2 loaded endothelial cells, and ii) the associated release of nitric oxide (NO) and von Willebrand factor (vWf). NO was measured either indirectly by radioimmunoassay of cGMP in unstimulated cells or directly by electrochemistry at the surface of stimulated endothelial cells from human umbilical cord veins (HUVEC). Short-term treatment of unstimulated HUVEC with intact i.v.Ig decreased the basal cytosolic Ca(2+) concentration by 20% while it activated the NO/cGMP synthesis. Following i.v.Ig treatment of HUVEC, the Ca(2+) liberation from internal stores and the vWf secretion induced by ATP, thrombin or histamine were significantly reduced by 38 and 60%, respectively. The effects on Ca(2+) signals were observed with intact i.v.Ig as well as with the F(ab')2 or the Fc fragments indicating that both portions are involved in the mechanism of action. The i.v.Ig treatment of HUVECs had no effect on the NO release induced by thrombin or histamine. By contrast, the i.v.Ig treatment increased the ATP-activated NO release by amplifying the Ser1177-eNOS phosphorylation. The i.v.Ig also activated the NO-dependent cGMP release in resting and collagen-stimulated platelets. Since NO is a potent inhibitor of platelet activation and vWF is a platelet adhesion cofactor, the beneficial effects of therapeutic i.v.Ig may lie in the inhibition of platelet adhesion to damaged endothelium.