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Thromb Haemost 2010; 104(06): 1235-1241
DOI: 10.1160/TH10-02-0102
Cellular Proteolysis and Oncology
Schattauer GmbH

Daunorubicin induces procoagulant activity of cultured endothelial cells through phosphatidylserine exposure and microparticles release

Yueyue Fu   *
1   Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Jin Zhou   *
1   Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Huibo Li
1   Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Fenglin Cao
1   Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Yanhua Su
1   Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Shengjin Fan
1   Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Yinghua Li
1   Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Shuye Wang
1   Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Limin Li
1   Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Gary E. Gilbert
2   Medicine Departments of VA Boston Healthcare System, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts, USA
,
Jialan Shi
1   Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
2   Medicine Departments of VA Boston Healthcare System, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts, USA
› Author Affiliations Financial support: This work was supported by the National Natural Science Foundation of China (30871227), the National Traditional Chinese Medicine Bureau (0607LP15), the International Cooperation Foundation (WH05C01), the Scientific Foundation of Heilongjiang Province (GB08C401–02), and the Health Department Foundation of Heilongjiang Province (2009–548, 2009–549).
Further Information

Publication History

Received: 07 February 2010

Accepted after minor revision: 13 September 2010

Publication Date:
24 November 2017 (online)

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Summary

Administration of various chemotherapeutic agents is associated with an increased risk of thrombotic events. Although vascular endothelium plays a predominant role in blood coagulation and fibrinolysis, the effect of cytotoxic drugs on the procoagulant activity (PCA) of endothelial cells has not been well evaluated. Our study aims to investigate the possibility that daunorubicin, a chemotherapeutic agent, exerts prothrombotic effect on endothelial cells. We tested the impact of daunorubicin on phosphatidylserine (PS) exposure, endothelial microparticles (EMPs) release and consequent PCA. Human umbilical vein endothelial cells (HUVECs) were treated with daunorubicin (0.1, 0.2, 0.5, 1, 2 μM) for 24 hours. PCA of HUVECs was measured using clotting time and purified coagulation complex assays. Counts and PCA of EMPs were evaluated by flow cytometry and clotting time assay, respectively. Lactadherin was used as a novel probe for detection of PS exposure and EMPs release. We found that daunorubicin dose-dependently increased the PS exposure and consequent PCA of HUVECs. Moreover, daunorubicin treatment also enhanced the release of EMPs which were highly procoagulant. This increment was especially significant at 0.2 μM of daunorubicin or more. Blockade of PS with lactadherin inhibited over 90% of HUVECs and EMPs PCA. However, anti-TF antibody had no significant inhibition effect. Our results demonstrate that daunorubicin treatment enhanced PCA of HUVECs through PS exposure and shedding of procoagulant EMPs. Lactadherin acts as an efficient anticoagulant in this process.

Keywords

Daunorubicin - endothelial cells - phosphatidylserine - microparticles - lactadherin

* Theses authors contributed equally.


 

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