Abstract
BackgroundSex differences in incidence of cardiovascular disease may reflect age-associated intravascular cellular activation resulting in shedding of cell membrane-derived bioactive microvesicles (MV or microparticles) into the blood. Concentrations of cell-specific MV in blood have the potential to be a diagnostic/prognostic marker of pathology, but ranges of MV must first be established in healthy individuals. This study identified cellular origin of blood-borne MV >0.2 μm in blood of apparently healthy women and men aged from 20–70 years.MethodsVenous blood from apparently healthy participants in the Mayo Clinic Biobank was collected into tubes containing protease inhibitors as the anticoagulant. MV were isolated by standardized differential centrifugation and characterized by digital flow cytometer. Each cellular origin of MV was verified by two different antibodies with strong correlation between the two distinct antibodies (e.g., for platelet-derived MV, r2 = 0.97).ResultsMV derived from platelets were the most abundant type of MV in blood from women and men in all age groups. Total numbers of phosphatidylserine, P-selectin, and platelet- and endothelium-derived MV were significantly (P < 0.05) greater in women than men. Numbers of MV from erythrocytes and stem/progenitor cells were significantly lower in premenopausal women than age-matched men. Number of tissue factor pathway inhibitor positive MV were significantly (P < 0.05) lower whereas erythrocyte-derived MV were significantly higher in postmenopausal women compared to premenopausal women. In women, there was a positive relationship between age and erythrocyte-derived MV (ρ = 0.28; P = 0.009), while in men adipocyte-derived MV increased with age (ρ = 0.33; P = 0.01).ConclusionsThis study provides ranges for cellular origin of blood-borne MV in age-matched, apparently healthy women and men from which to compare diagnostic and prognostic uses of blood-borne MV in larger studies and patient population. In addition, sex- and age-specific differences in phosphatidylserine, platelet-, endothelium-, erythrocyte-, and adipocyte-derived blood-borne MV may contribute to differential progression of cardiovascular disease in women compared to men.
Highlights
Sex differences in incidence of cardiovascular disease may reflect age-associated intravascular cellular activation resulting in shedding of cell membrane-derived bioactive microvesicles (MV or microparticles) into the blood
A comparison of premenopausal women with agematched men showed that phosphatidylserine and P-selectin positive MV were higher in women whereas there were no statistically significant differences in tissue factor, tissue factor pathway inhibitor, and cellular
This study provides the ranges of MV positive for molecules involved in procoagulation, anticoagulation, cellular adhesion, and the cellular origin of MV in apparently healthy women and men between the ages of 20–70 years
Summary
Sex differences in incidence of cardiovascular disease may reflect age-associated intravascular cellular activation resulting in shedding of cell membrane-derived bioactive microvesicles (MV or microparticles) into the blood. This study identified cellular origin of blood-borne MV >0.2 μm in blood of apparently healthy women and men aged from 20–70 years. Microvesicles (MV or microparticles) are submicron-size sealed vesicles shed from the plasma membrane of activated cells. Most MV originating from activated cells carry surface phosphatidylserine, a type of negatively charged phospholipid that acts as a catalytic site for the generation of thrombin that is required for the conversion of fibrinogen to fibrin clots [9,10]. MV originating from activated platelets, leukocytes, erythrocytes, and endothelial cells have been linked to cardiovascular and thrombotic complications and other diseases [4,7,10,11].
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