Age- and sex-specific differences in blood-borne microvesicles from apparently healthy humans

Callie M. Gustafson, Alex J. Shepherd, Virginia M Miller, Muthuvel Jayachandran

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: 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. 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. Methods: Venous 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, r 2∈=∈0.97). Results: MV 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). Conclusions: This 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.

Original languageEnglish (US)
Article number10
JournalBiology of Sex Differences
Volume6
Issue number1
DOIs
StatePublished - May 11 2015

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Sex Characteristics
Blood Platelets
Erythrocytes
Phosphatidylserines
Adipocytes
Endothelium
diagnostic
Cardiovascular Diseases
Stem Cells
Disease
Erythrocyte Count
P-Selectin
Antibodies
Protease Inhibitors
Centrifugation
pathology
Anticoagulants
activation
age group
Healthy Volunteers

Keywords

  • Anticoagulant vesicles
  • Extracellular vesicles
  • Flow cytometry
  • Microparticles
  • Procoagulant vesicles
  • Sex differences

ASJC Scopus subject areas

  • Gender Studies
  • Endocrinology

Cite this

Age- and sex-specific differences in blood-borne microvesicles from apparently healthy humans. / Gustafson, Callie M.; Shepherd, Alex J.; Miller, Virginia M; Jayachandran, Muthuvel.

In: Biology of Sex Differences, Vol. 6, No. 1, 10, 11.05.2015.

Research output: Contribution to journalArticle

Gustafson, Callie M. ; Shepherd, Alex J. ; Miller, Virginia M ; Jayachandran, Muthuvel. / Age- and sex-specific differences in blood-borne microvesicles from apparently healthy humans. In: Biology of Sex Differences. 2015 ; Vol. 6, No. 1.
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abstract = "Background: 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. 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. Methods: Venous 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, r 2∈=∈0.97). Results: MV 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). Conclusions: This 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.",
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AU - Jayachandran, Muthuvel

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N2 - Background: 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. 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. Methods: Venous 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, r 2∈=∈0.97). Results: MV 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). Conclusions: This 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.

AB - Background: 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. 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. Methods: Venous 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, r 2∈=∈0.97). Results: MV 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). Conclusions: This 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.

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KW - Procoagulant vesicles

KW - Sex differences

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