Abstract 525: New Candidate Biomarkers for Cardiovascular Risk in Early Menopausal Women
Little is known about the cellular mechanisms by which estrogen deprivation with menopause contributes to thrombosis and associated cardiovascular events. Experiments were designed to examine the relationships among circulating estrogen, the cellular origin of circulating microparticles (microvesicles) and procoagulant activity in early menopausal women being screened for the Kronos Early Estrogen Prevention Study. Blood microparticles (Mps) were isolated by differential centrifugation and identified by flow cytometry (FACS Canto™) using cell-specific antibodies. Circulating estrogen levels are catalogued as low (Group L, <20pg/mL; n=21) or high (Group H, >40pg/mL; n= 11). Age, body weight, BMI, blood pressure, total cholesterol, LDL, HDL, triglycerides, blood glucose, TSH and hs-CRP levels were the same in both groups. None was hypertensive, diabetic or current smoker and all were <10% risk by Framingham Score. Months into menopause (20 ± 2.0 vs 13 ± 2.1 mo) and FSH (89 ± 7.6 vs 52 ± 5.8 mIU/L) were lower, whereas activated protein C (0.4 ± 0.1 vs 0.9 ± 0.2ng/mL) was higher, in Group H. Platelet counts, basal, thrombin receptor agonist peptide (TRAP) and adenosine diphosphate (ADP) activated P-selectin expression on platelet membranes did not change, but TRAP and ADP activated glycoprotein IIb/IIIa expression (% positive; 9.0 ± 1.3 vs 19 ± 4.6; 67 ± 2.9 vs 82 ± 2.8 respectively) were greater in Group H. Of the total procoagulant (phosphatidylserine positive Mps, 144 ± 29 vs 64 ± 25 Mp/μL), those from monocytes (12 ± 2.5 vs 6 ± 1.5 Mp/μL), granulocytes (16 ± 5.2 vs 12 ± 4.4 Mp/μL), platelets (127 ± 31.7 vs 51 ± 22.5 Mp/μL) and endothelium-(22 ± 3.8 vs 12 ± 1.7 Mp/μL) and those bearing tissue factor (8.7 ± 4.2 vs 0.5 ± 0.2 Mp/μL) were greater in Group L. These results suggest that, with declines in endogenous estrogen at menopause, monocyte, platelet and endothelium shed excess procoagulant microparticles. Microparticles have potential for use in new diagnostic and therapeutic strategies for risk stratification and therapeutic interventions in early menopausal women usually considered at low risk for cardiovascular disease (HL78638, AHA30503Z, HL90639, Kronos Longevity Institute and Mayo Foundation).
This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).