High risk oral contraceptive hormones do not directly enhance endothelial cell procoagulant activity in vitro

Author:

Bouck Emma G.ORCID,Arvanitis Marios,Osburn William O.,Sang Yaqiu,Reventun Paula,Ahmadzia Homa K.,Smith Nicholas L.,Lowenstein Charles J.,Wolberg Alisa S.ORCID

Abstract

BackgroundOral contraceptive (OC) use increases venous thromboembolism risk 2-5-fold. Procoagulant changes can be detected in plasma from OC users even without thrombosis, but cellular mechanisms that provoke thrombosis have not been identified. Endothelial cell (EC) dysfunction is thought to initiate venous thromboembolism. It is unknown whether OC hormones provoke aberrant procoagulant activity in ECs.ObjectiveCharacterize the effect of high-risk OC hormones (ethinyl estradiol [EE] and drospirenone) on EC procoagulant activity and the potential interplay with nuclear estrogen receptors ERα and ERβ and inflammatory processes.MethodsHuman umbilical vein and dermal microvascular ECs (HUVEC and HDMVEC, respectively) were treated with EE and/or drospirenone. Genes encoding the estrogen receptors ERα and ERβ (ESR1andESR2, respectively) were overexpressed in HUVEC and HDMVEC via lentiviral vectors. EC gene expression was assessed by RT-qPCR. The ability of ECs to support thrombin generation and fibrin formation was measured by calibrated automated thrombography and spectrophotometry, respectively.ResultsNeither EE nor drospirenone, alone or together, changed expression of genes encoding anti- or procoagulant proteins (TFPI,THBD,F3), integrins (ITGAV,ITGB3), or fibrinolytic mediators (SERPINE1,PLAT). EE and/or drospirenone did not increase EC-supported thrombin generation or fibrin formation, either. Our analyses indicated a subset of individuals expressESR1andESR2transcripts in human aortic ECs. However, overexpression ofESR1and/orESR2in HUVEC and HDMVEC did not facilitate the ability of OC-treated ECs to support procoagulant activity, even in the presence of a pro-inflammatory stimulus.ConclusionsThe OC hormones EE and drospirenone do not directly enhance thrombin generation potential of primary ECsin vitro.

Funder

National Heart, Lung, and Blood Institute

National Institute of General Medical Sciences

Publisher

Public Library of Science (PLoS)

Subject

Multidisciplinary

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