Paradoxical influence of estrogenic hormones on platelet-endothelial cell interactions

• Published in: Thrombosis research Vol. 74; no. 6; pp. 577 - 594
• Main Authors: Miller, Marilyn E., Dores, Graça M., Thorpe, Susan L., Akerley, Wallace L.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 15.06.1994; Elsevier Science
• Subjects: Biological and medical sciences; Blood and lymphatic vessels; Blood Platelets - cytology; Blood Platelets - drug effects; Cardiology. Vascular system; Cell Communication - drug effects; Cell Division - drug effects; Cells, Cultured; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Estradiol - pharmacology; estrogen; Female; human endothelial cells; Humans; Male; Medical sciences; Miscellaneous; platelet adhesion; Platelet Aggregation - drug effects; Regional Blood Flow - drug effects; tamoxifen; Tamoxifen - pharmacology; thrombosis; Thrombosis - physiopathology; estrogen; thrombosis; human endothelial cells; platelet adhesion; tamoxifen; Antineoplastic agent; Human; Hormone; Endothelial cell; Antiestrogen; Estrogen; Cell cell interaction; Antihormone; Adhesion; Thrombosis; Tamoxifene; Platelet; Etiology
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/0049-3848(94)90215-1

Controversies abound in the literature about the safety and efficacy of tamoxifen and estrogen. We studied the effect of these 2 hormonal agents on factors involved in in vitro thrombogenesis: platelets and endothelial cells. Endothelial cells were derived from human umbilical veins and platelets were obtained from premenopausal and postmenopausal women, women on oral contraceptives, postmenopausal women on hormone replacement therapy, men, and patients with breast cancer who had been taking adjuvant tamoxifen for more than 1 year. The interaction of platelets with endothelial cell matrix was measured in 2 systems: 1) in a flow chamber at low shear rate and, 2) with 51Cr labeled platelets in a “static” culture system. In the static system, platelets from women on tamoxifen exhibited decreased platelet adherence to endothelial cell matrix whether they were grown in tamoxifen or control conditions, when compared to platelets from premenopausal women. When flow (25 sec −1) was added these differences were negated. Neither tamoxifen nor 17β estradiol had an effect on endothelial cell proliferation or platelet aggregation. Adhesion of platelets at low shear was not altered when platelet rich plasma was incubated with tamoxifen nor when endothelial cells were grown in tamoxifen. In contrast, incubation of platelets in 17β estradiol decreased platelet adhesion at low shear rate, however, there was no effect on platelet adhesion when endothelial cells were grown in 17β estradiol. We conclude that in early stages of thrombus formation as measured in vitro, tamoxifen may not have a detrimental effect and estrogen may be protective.