TY - JOUR
T1 - Alterations in platelet function and cell-derived microvesicles in recently menopausal women
T2 - Relationship to metabolic syndrome and atherogenic risk
AU - Jayachandran, Muthuvel
AU - Litwiller, Robert D.
AU - Lahr, Brian D.
AU - Bailey, Kent R.
AU - Owen, Whyte G.
AU - Mulvagh, Sharon L.
AU - Heit, John A.
AU - Hodis, Howard N.
AU - Harman, S. Mitchell
AU - Miller, Virginia M.
N1 - Funding Information:
Acknowledgments This work was supported by grants from the Aurora Foundation to the Kronos Longevity Research Institute, NIH HL90639, 1UL1 RR0241501, American Heart Association–Scientist Development Grant, AHA 08-30503Z, and the Mayo Foundation. The authors thank the dedicated volunteers participating in this study and co-workers who made this possible, including Phillip A. Araoz, MD, Rebecca Beck, RN, Teresa G. Zais, and the staff in the Women’s Health Clinic.
PY - 2011/12
Y1 - 2011/12
N2 - A woman's risk for metabolic syndrome (MS) increases at menopause, with an associated increase in risk for cardiovascular disease. We hypothesized that early menopause-related changes in platelet activity and concentrations of microvesicles derived from activated blood and vascular cells provide a mechanistic link to the early atherothrombotic process. Thus, platelet functions and cellular origin of blood-borne microvesicles in recently menopausal women (n = 118) enrolled in the Kronos Early Estrogen Prevention Study were correlated with components of MS and noninvasive measures of cardiovascular disease [carotid artery intima medial thickness (CIMT), coronary artery calcium (CAC) score, and endothelial reactive hyperemic index (RHI)]. Specific to individual components of the MS pentad, platelet number increased with increasing waist circumference, and platelet secretion of ATP and expression of P-selectin decreased with increasing blood glucose (p = 0.005) and blood pressure (p < 0.05), respectively. Waist circumference and systolic blood pressure were independently associated with monocyte- and endothelium-derived microvesicles (p < 0.05). Platelet-derived and total procoagulant phosphatidylserine-positive microvesicles, and systolic blood pressure correlated with CIMT (p < 0.05), but not with CAC or RHI. In summary, among recently menopausal women, specific platelet functions and concentrations of circulating activated cell membrane-derived procoagulant microvesicles change with individual components of MS. These cellular changes may explain in part how menopause contributes to MS and, eventually, to cardiovascular disease.
AB - A woman's risk for metabolic syndrome (MS) increases at menopause, with an associated increase in risk for cardiovascular disease. We hypothesized that early menopause-related changes in platelet activity and concentrations of microvesicles derived from activated blood and vascular cells provide a mechanistic link to the early atherothrombotic process. Thus, platelet functions and cellular origin of blood-borne microvesicles in recently menopausal women (n = 118) enrolled in the Kronos Early Estrogen Prevention Study were correlated with components of MS and noninvasive measures of cardiovascular disease [carotid artery intima medial thickness (CIMT), coronary artery calcium (CAC) score, and endothelial reactive hyperemic index (RHI)]. Specific to individual components of the MS pentad, platelet number increased with increasing waist circumference, and platelet secretion of ATP and expression of P-selectin decreased with increasing blood glucose (p = 0.005) and blood pressure (p < 0.05), respectively. Waist circumference and systolic blood pressure were independently associated with monocyte- and endothelium-derived microvesicles (p < 0.05). Platelet-derived and total procoagulant phosphatidylserine-positive microvesicles, and systolic blood pressure correlated with CIMT (p < 0.05), but not with CAC or RHI. In summary, among recently menopausal women, specific platelet functions and concentrations of circulating activated cell membrane-derived procoagulant microvesicles change with individual components of MS. These cellular changes may explain in part how menopause contributes to MS and, eventually, to cardiovascular disease.
KW - Atherosclerosis
KW - Carotid intima medial thickening
KW - Coronary calcification
KW - Endothelial function
KW - Monocytes
KW - Platelet secretion
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U2 - 10.1007/s12265-011-9296-9
DO - 10.1007/s12265-011-9296-9
M3 - Article
C2 - 21786187
AN - SCOPUS:81855176108
SN - 1937-5387
VL - 4
SP - 811
EP - 822
JO - Journal of cardiovascular translational research
JF - Journal of cardiovascular translational research
IS - 6
ER -