Deficiency of LRP8 in mice is associated with altered platelet function and prolonged time for in vivo thrombosis.

Thrombosis Research
Jason O RobertsonJonathan D Smith

Abstract

Our group has previously reported genetic studies associating polymorphisms in the low density lipoprotein receptor related protein 8 (LRP8) gene with myocardial infarction. The aim of this study was to define the role of platelet surface LRP8 in thrombosis. Flow cytometry, aggregometry, intravital microscopy and tail bleeding assays were used to examine platelet function and hemostasis in LRP8-deficient mice and littermate controls. We demonstrated that activation of platelets from both LRP8(+/-) and LRP8(-/-) mice was reduced in vitro in response to either ADP or thrombin. In vivo, LRP8-hemizygous and LRP8(-/-) mice demonstrated 200% and 68% increased time for carotid occlusion in response to FeCl(3) injury, respectively. Moreover, lipidated apoE3, a ligand for LRP8, inhibited platelet activation in a dose-dependent fashion. This inhibition was markedly attenuated in LRP8(-/-) but not LRP8(+/-) mice and did not result from membrane cholesterol efflux or a nitric oxide dependent pathway. Tail bleeding times were unaffected in both genotypes. Our results suggest that LRP8 is capable of altering thrombosis without affecting normal hemostasis through mechanisms both dependent on and independent of apoE. This suggests a means wher...Continue Reading

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Citations

Oct 19, 2011·Journal of Thrombosis and Thrombolysis·Luís Cavalcante NagatoDorotéia Rossi Silva Souza
Apr 20, 2010·The Journal of Biological Chemistry·James L DanielArchana Sanjay
Jun 15, 2011·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Honggang RenYu Hu
May 18, 2016·Trends in Parasitology·Magda Vieira BenavidesCurtis Van Tassell
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Dec 14, 2019·Cardiovascular Research·Chieko Mineo
Jul 16, 2020·International Journal of Molecular Sciences·Jeremy LagrangePhilip Wenzel

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