[Show abstract][Hide abstract] ABSTRACT: Physical inactivity promotes the development of cardiovascular diseases. However, few data exist examining the vascular consequences of short-term reductions in daily physical activity. Thus, we tested the hypothesis that popliteal and brachial artery flow-mediated dilation (FMD) would be reduced and concentrations of endothelial microparticles (EMPs) would be elevated following reduced daily physical activity. To examine this, popliteal and brachial artery FMD and plasma levels of EMPs suggestive of apoptotic and activated endothelial cells (CD31(+)/CD42b(-) and CD62E(+) EMPs, respectively) were measured at baseline and during days 1,3, and 5 of reduced daily physical activity in 11 recreationally active men (25±2 yrs). Subjects were instructed to reduce daily physical activity by taking <5,000 steps/day and refraining from planned exercise. Popliteal artery FMD decreased with reduced activity (Baseline: 4.7±0.98%, Reduced Activity Day 5: 1.72±0.68%, p<0.05), while brachial artery FMD was unchanged. In contrast, baseline (pre FMD) popliteal artery diameter did not change whereas, brachial artery diameter decreased (Baseline: 4.35±0.12, Reduced Activity Day 5: 4.12±0.11 p<0.05) following 5 days of reduced daily physical activity. CD31(+)/CD42b(-) EMPs were significantly elevated with reduced activity (Baseline: 17.6 ± 9.4, Reduced Activity Day 5: 104.1±43.1 per μL plasma, p<0.05), whereas CD62E(+) EMPs were unaltered. Collectively, our results provide evidence for the early and robust deleterious impact of reduced daily activity on vascular function and highlight the vulnerability of the vasculature to a sedentary lifestyle.
Journal of Applied Physiology 09/2013; · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endothelium-derived microparticles (EMPs) are submicron vesicles released from the plasma membrane of endothelial cells in response to injury, apoptosis or activation. We have previously demonstrated EMP-induced acute lung injury (ALI) in animal models and endothelial barrier dysfunction in vitro. Current treatment options for ALI are limited and consist of supportive therapies. We hypothesize that standard clinical continuous venovenous hemofiltration (CVVH) reduces serum EMP levels and may be adapted as a potential therapeutic intervention.
EMPs were generated from plasminogen activation inhibitor-1 (PAI-1)-stimulated human umbilical vein endothelial cells (HUVECs). Flow cytometric analysis was used to characterize EMPs as CD31- and annexin V-positive events in a submicron size gate. Enumeration was completed against a known concentration of latex beads. Ultimately, a concentration of ~650,000 EMP/mL perfusate fluid (total 470 mL) was circulated through a standard CVVH filter (pore size 200 μm, flow rate 250 mL/hr) for a period of 70 minutes. 0.5 mL aliquots were removed at 5- to 10-minute intervals for flow cytometric analysis. EMP concentration in the dialysate was measured at the end of 4 hours to better understand the fate of EMPs.
A progressive decrease in circulating EMP concentration was noted using standard CVVH at 250 mL/hr (a clinical standard rate) from a 470 mL volume modelling a patient's circulation. A 50% reduction was noted within the first 30 minutes. EMPs entering the dialysate after 4 hours were 5.7% of the EMP original concentration.
These data demonstrate that standard CVVH can remove EMPs from circulation in a circuit modelling a patient. An animal model of hemofiltration with induction of EMP release is required to test the therapeutic potential of this finding and potential of application in early treatment of ALI.
[Show abstract][Hide abstract] ABSTRACT: Microparticles (MPs), small membrane-derived vesicles, are derived from many cell types and released into the circulation. Microparticles can express antigens, and contain cell surface proteins, cytoplasmic contents, and nuclear components from their cell of origin that determines their composition, characterization, and transfer of biologic information. Certain prompts for this release include shear stress, complement activation, proapoptotic stimulation, cellular damage, or agonist interaction with cell surface receptors. Release can be physiologic or pathologic and is associated with proinflammatory and procoagulant effects and has been implicated in thrombotic states. Microparticles also contribute to systemic inflammation and cardiovascular, hematologic, and oncologic disease states. The study of MPs in human medicine is rapidly advancing and extends into the physiology of health, the pathophysiology of disease, and the role of MPs in transfusion medicine. In veterinary medicine, published work on MPs has been limited to the area of inherited disorders, blood storage, and leukoreduction (LR). Microparticle research is still in its infancy, and this review should be seen as a snapshot of what is currently known. As research continues important limitations, including variations in preanalytic variables such as collection, storage, or centrifugation, and limitations of quantitation are coming to the forefront. Correlation of quantitation of MPs with assays of activity will hopefully shed light on the true nature of MPs in health and disease. This review will focus on the role of cellular exocytic vesiculation in health, disease, and transfusion medicine.
Journal of Veterinary Internal Medicine 07/2013; · 2.06 Impact Factor
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