Chronic venous insufficiency is associated with elevated level of circulating microparticles

Abstract

Summary. Background: Chronic venous insufficiency (CVI) results when the veins in the legs no longer pump blood back to the heart effectively. Microparticles (MPs) are small membrane vesicles released by several circulating and vascular cells upon activation or apoptosis. Objectives: The purpose of this study was to assess the subpopulations of circulating endothelial (EMPs) and platelet microparticles (PMPs) in CVI, and to disclose their contribution in mediating dysfunction of human peripheral venules. Patients and methods: Human peripheral venules were explanted during leg surgery on patients with CVI and on control subjects (C); concurrently, blood samples were collected and circulating MPs isolated. The techniques used were: flow cytometry, fluorescence and electron microscopy, myograph technique and western-blotting technique. Results: The results showed that compared with controls, patients with CVI had: (i) a marked elevation of circulating EMPs and PMPs; (ii) a structural modification of the venous wall consisting of activation of endothelial and smooth muscle cells, an abundance of intermediary filaments and synthesis of hyperplasic-multilayered basal lamina; (iii) a significantly altered reactivity of the venous wall, closely associated with EMPs and PMPs adherence; (iv) altered contractile response to noradrenaline, acetylcholine, 5-hydroxytryptamine and KCl, and an impeded relaxation in response to sodium nitroprusside; and (iv) a substantially increased protein expression of tissue factor (TF) and of P-Selectin both in the venular vascular wall and on the surface of EMPs and PMPs. Conclusions: The findings indicate that CVI is accompanied by an enhanced release of EMPs and PMPs that contribute to altered dysfunctional response of the venous wall.

Circulating Endothelial Progenitor Cell and Platelet Microparticle Impact on Platelet Activation in Hypertension Associated with Hypercholesterolemia

“…Plasma PMPs were separated according to the method reported by Georgescu et al [5], [26]. Briefly, the procedure consists in collection of venous blood in 0.138 M tri–sodium citrate 9/1 (vol/vol), centrifugation at 1000× g for 15 min, at 15°C and separation of platelet rich plasma (PRP).…”

“…PMPs were sorted from PFP according to Georgescu et al [5], [26] using specific antibodies to integrin αIIb (M 148) PE (for CD41) and annexin V FITC (for PS) and the MoFlo flow cytometer (Dako, USA) equipped with high-speed cell sorter. The number of PMPs was adjusted at 1×10 5 /ml in PBS.…”

“…Platelet microparticles (PMPs) are the most abundant microparticles in the bloodstream constituting approximately 70% to 90% of circulating microparticles [25]. Elevated PMPs levels are found in the blood of patients with diseases associated with thrombosis, for example: heparin-induced thrombocytopenia, arterial thrombosis, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenia, sickle cell disease, uremia, chronic venous insufficiency, hypertension associated with hypercholesterolemia [5], [25], [26].…”

Proteomics of microparticles after deep venous thrombosis

“…MP may concentrate certain proteins, and have been characterized by evaluating platelet-derived and plasma-derived MP obtained from healthy individuals 6, 7. Fibrinogen was enriched on MP in a nonhuman primate model of venous thrombosis8 9.However, there has been no description of MP protein up-regulation or depletion on human MP in patients with venous thrombosis. Therefore, the purpose of this study was to use proteomic evaluation to identify these proteins, helping to understand the role of MP in human venous thrombogenesis.…”

Low‐dose aspirin as an adjuvant treatment for venous leg ulceration: study protocol for a randomized controlled trial (Aspirin4VLU)

“…Patients with CVI have significantly higher platelet counts compared with normal controls or people with non‐venous leg ulcers (Goodfield , Georgescu et al . ). Platelets in patients with CVI also have increased reactivity compared with normal controls (Lu et al .…”