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Arsenite-enhanced procoagulant activity through phosphatidylserine exposure in platelets

Title
Arsenite-enhanced procoagulant activity through phosphatidylserine exposure in platelets
Author
배옥남
Issue Date
2007-12
Publisher
AMER CHEMICAL SOC
Citation
CHEMICAL RESEARCH IN TOXICOLOGY, v. 20, No. 12, Page. 1760-1768
Abstract
Numerous epidemiological studies have reported the close relationship between arsenic in drinking water and cardiovascular disease (CVD), yet the exact mechanism underlying this relationship remains unclear. We investigated whether arsenic can affect the procoagulant activity of platelets, which are essential in blood clotting, thrombus formation, and progression of CVD. While arsenite alone did not induce procoagulant activity, it significantly enhanced thrombin-induced procoagulant activity of human platelets in a concentration- and time-dependent manner. In flow cytometric analysis, arsenite potentiated phosphatidylserine (PS) exposure and microparticle (MP) formation, the major mediators of procoagulant activity. Arsenite-enhanced calcium increase and subsequent calpain activation were found to be involved in these effects, as determined by confocal microscopy and gel electrophoresis. Arsenite also inhibited flippase, an enzyme that restores PS to the inner leaflet, suggesting that PS could be retained in outer membranes after exposure. Consistent with these in vitro results, ex vivo studies revealed that PS exposure in platelets was significantly increased after acute or chronic arsenic exposure in rats. Most notably, in a rodent in vivo venous thrombosis model, arsenite indeed led to increased thrombus formation. In conclusion, arsenite-enhanced procoagulant activity in platelets by PS exposure and MP generation ultimately results in accelerated thrombus formation in vivo, suggesting that this enhanced activity is a possible contributing factor in CVD associated with chronic exposure to arsenic through drinking water.
URI
https://pubs.acs.org/doi/abs/10.1021/tx700159yhttps://repository.hanyang.ac.kr/handle/20.500.11754/107572
ISSN
0893-228X; 1520-5010
DOI
10.1021/tx700159y
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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