In Vivo exposure of lipopolysaccharide (LPS) but not estrogen decreases platelet reactivity in early postmenopausal women

Abstract

Infection and oral estrogen treatments are risk factors for thrombosis. Experiments were designed to evaluate in vitro effects of priming doses of LPS and physiological doses of estrogen on platelets from healthy, newly menopausal women. Blood was collected from early postmenopausal women (42–56 years old) with a menopausal age between 6 months to 3 years into anticoagulants (citrate, hirudin and TAP). Platelet rich plasma was prepared and preincubated with LPS (ultrapure LPS from E. Coli: 10ng-1000ng/mL) and/or 17β-estradiol(10−10M/mL) Four groups were studied: control, LPS, 17β-estradiol, 17β-estradiol+LPS). Platelet aggregation was measured by lumiaggregometry. Thrombin receptor agonist peptide (TRAP 10μM) was used as an agonist. Platelet dense granules ATP secretion was measured by luciferin bioluminescence. Only the highest concentration of LPS (100ng/ml) decreased the maximum and rate of ATP secretion from dense granules and aggregation. At physiological concentrations, 17β-estradiol did not affect platelet aggregation alone or in combination with LPS. These data suggest that LPS and estrogen may not increase thrombotic risk by direct activation of platelets; effects most likely require the interaction of the platelets with other cells in the circulation. (Supported by NIH HL78638, the Mayo Foundation, Kronos Longevity Institute and Japanese Menopause Society)