Characterization of blood borne microparticles as markers of premature coronary calcification in newly menopausal women

Muthuvel Jayachandran, Robert D. Litwiller, Whyte G. Owen, John A. Heit, Thomas Behrenbeck, Sharon L. Mulvagh, Philip A Araoz, Matthew J. Budoff, S. Mitchell Harman, Virginia M Miller

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

While the risk for symptomatic atherosclerotic disease increases after menopause, currently recognized risk factors do not identify ongoing disease processes in low-risk women. This study tested the hypothesis that circulating cell-derived microparticles may reflect disease processes in women defined as low risk by the Framingham risk score. The concentration and phenotype of circulating microparticles were evaluated in a cross-sectional study of apparently healthy menopausal women, screened for enrollment into the Kronos Early Estrogen Prevention Study. Microparticles were evaluated by flow cytometry, and coronary artery calcification (CAC) was scored using 64-slice computed tomography scanners. The procoagulant activity of isolated microparticles was determined with a sensitive fluorescent thrombin generation assay. Chronological age, body mass index, serum lipids, systolic blood pressure (Framingham risk score < 10%, range 1-3%), and high-sensitivity C-reactive protein did not differ significantly among women with low (0 < 35; range, 0.3-32 Agatston units) or high (>50; range, 93-315 Agatston units) CAC compared with women without calcification. The total concentration and percentage of microparticles derived from platelets and endothelial cells were greatest in women with high CAC scores. The thrombin-generating capacity of the isolated microparticles correlated with phosphatidylserine expression, which also was greatest in women with high CAC scores. The percentages of microparticles expressing granulocyte and monocyte markers were not significantly different among groups. Therefore, the characterization of platelet and endothelial microparticles may identify early menopausal women with premature CAC who would not otherwise be identified by the usual risk factor analysis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume295
Issue number3
DOIs
StatePublished - Sep 2008

Fingerprint

Coronary Vessels
Thrombin
Cell-Derived Microparticles
Blood Platelets
X-Ray Computed Tomography Scanners
Blood Pressure
Phosphatidylserines
Menopause
Granulocytes
Statistical Factor Analysis
Monocytes
Flow Cytometry
Estrogens
Body Mass Index
Endothelial Cells
Cross-Sectional Studies
Phenotype
Lipids
Serum

Keywords

  • Phosphatidylserine
  • Procoagulant activity
  • Thrombosis

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Characterization of blood borne microparticles as markers of premature coronary calcification in newly menopausal women. / Jayachandran, Muthuvel; Litwiller, Robert D.; Owen, Whyte G.; Heit, John A.; Behrenbeck, Thomas; Mulvagh, Sharon L.; Araoz, Philip A; Budoff, Matthew J.; Harman, S. Mitchell; Miller, Virginia M.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 295, No. 3, 09.2008.

Research output: Contribution to journalArticle

Jayachandran, Muthuvel ; Litwiller, Robert D. ; Owen, Whyte G. ; Heit, John A. ; Behrenbeck, Thomas ; Mulvagh, Sharon L. ; Araoz, Philip A ; Budoff, Matthew J. ; Harman, S. Mitchell ; Miller, Virginia M. / Characterization of blood borne microparticles as markers of premature coronary calcification in newly menopausal women. In: American Journal of Physiology - Heart and Circulatory Physiology. 2008 ; Vol. 295, No. 3.
@article{1157ddf463894bf999dd0ba6a6988511,
title = "Characterization of blood borne microparticles as markers of premature coronary calcification in newly menopausal women",
abstract = "While the risk for symptomatic atherosclerotic disease increases after menopause, currently recognized risk factors do not identify ongoing disease processes in low-risk women. This study tested the hypothesis that circulating cell-derived microparticles may reflect disease processes in women defined as low risk by the Framingham risk score. The concentration and phenotype of circulating microparticles were evaluated in a cross-sectional study of apparently healthy menopausal women, screened for enrollment into the Kronos Early Estrogen Prevention Study. Microparticles were evaluated by flow cytometry, and coronary artery calcification (CAC) was scored using 64-slice computed tomography scanners. The procoagulant activity of isolated microparticles was determined with a sensitive fluorescent thrombin generation assay. Chronological age, body mass index, serum lipids, systolic blood pressure (Framingham risk score < 10{\%}, range 1-3{\%}), and high-sensitivity C-reactive protein did not differ significantly among women with low (0 < 35; range, 0.3-32 Agatston units) or high (>50; range, 93-315 Agatston units) CAC compared with women without calcification. The total concentration and percentage of microparticles derived from platelets and endothelial cells were greatest in women with high CAC scores. The thrombin-generating capacity of the isolated microparticles correlated with phosphatidylserine expression, which also was greatest in women with high CAC scores. The percentages of microparticles expressing granulocyte and monocyte markers were not significantly different among groups. Therefore, the characterization of platelet and endothelial microparticles may identify early menopausal women with premature CAC who would not otherwise be identified by the usual risk factor analysis.",
keywords = "Phosphatidylserine, Procoagulant activity, Thrombosis",
author = "Muthuvel Jayachandran and Litwiller, {Robert D.} and Owen, {Whyte G.} and Heit, {John A.} and Thomas Behrenbeck and Mulvagh, {Sharon L.} and Araoz, {Philip A} and Budoff, {Matthew J.} and Harman, {S. Mitchell} and Miller, {Virginia M}",
year = "2008",
month = "9",
doi = "10.1152/ajpheart.00193.2008",
language = "English (US)",
volume = "295",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Characterization of blood borne microparticles as markers of premature coronary calcification in newly menopausal women

AU - Jayachandran, Muthuvel

AU - Litwiller, Robert D.

AU - Owen, Whyte G.

AU - Heit, John A.

AU - Behrenbeck, Thomas

AU - Mulvagh, Sharon L.

AU - Araoz, Philip A

AU - Budoff, Matthew J.

AU - Harman, S. Mitchell

AU - Miller, Virginia M

PY - 2008/9

Y1 - 2008/9

N2 - While the risk for symptomatic atherosclerotic disease increases after menopause, currently recognized risk factors do not identify ongoing disease processes in low-risk women. This study tested the hypothesis that circulating cell-derived microparticles may reflect disease processes in women defined as low risk by the Framingham risk score. The concentration and phenotype of circulating microparticles were evaluated in a cross-sectional study of apparently healthy menopausal women, screened for enrollment into the Kronos Early Estrogen Prevention Study. Microparticles were evaluated by flow cytometry, and coronary artery calcification (CAC) was scored using 64-slice computed tomography scanners. The procoagulant activity of isolated microparticles was determined with a sensitive fluorescent thrombin generation assay. Chronological age, body mass index, serum lipids, systolic blood pressure (Framingham risk score < 10%, range 1-3%), and high-sensitivity C-reactive protein did not differ significantly among women with low (0 < 35; range, 0.3-32 Agatston units) or high (>50; range, 93-315 Agatston units) CAC compared with women without calcification. The total concentration and percentage of microparticles derived from platelets and endothelial cells were greatest in women with high CAC scores. The thrombin-generating capacity of the isolated microparticles correlated with phosphatidylserine expression, which also was greatest in women with high CAC scores. The percentages of microparticles expressing granulocyte and monocyte markers were not significantly different among groups. Therefore, the characterization of platelet and endothelial microparticles may identify early menopausal women with premature CAC who would not otherwise be identified by the usual risk factor analysis.

AB - While the risk for symptomatic atherosclerotic disease increases after menopause, currently recognized risk factors do not identify ongoing disease processes in low-risk women. This study tested the hypothesis that circulating cell-derived microparticles may reflect disease processes in women defined as low risk by the Framingham risk score. The concentration and phenotype of circulating microparticles were evaluated in a cross-sectional study of apparently healthy menopausal women, screened for enrollment into the Kronos Early Estrogen Prevention Study. Microparticles were evaluated by flow cytometry, and coronary artery calcification (CAC) was scored using 64-slice computed tomography scanners. The procoagulant activity of isolated microparticles was determined with a sensitive fluorescent thrombin generation assay. Chronological age, body mass index, serum lipids, systolic blood pressure (Framingham risk score < 10%, range 1-3%), and high-sensitivity C-reactive protein did not differ significantly among women with low (0 < 35; range, 0.3-32 Agatston units) or high (>50; range, 93-315 Agatston units) CAC compared with women without calcification. The total concentration and percentage of microparticles derived from platelets and endothelial cells were greatest in women with high CAC scores. The thrombin-generating capacity of the isolated microparticles correlated with phosphatidylserine expression, which also was greatest in women with high CAC scores. The percentages of microparticles expressing granulocyte and monocyte markers were not significantly different among groups. Therefore, the characterization of platelet and endothelial microparticles may identify early menopausal women with premature CAC who would not otherwise be identified by the usual risk factor analysis.

KW - Phosphatidylserine

KW - Procoagulant activity

KW - Thrombosis

UR - http://www.scopus.com/inward/record.url?scp=54049113531&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54049113531&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00193.2008

DO - 10.1152/ajpheart.00193.2008

M3 - Article

C2 - 18621859

AN - SCOPUS:54049113531

VL - 295

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 3

ER -