Cargando…

An Antithrombotic Strategy by Targeting Phospholipase D in Human Platelets

Phospholipase D (PLD) is involved in many biological processes. PLD1 plays a crucial role in regulating the platelet activity of mice; however, the role of PLD in the platelet activation of humans remains unclear. Therefore, we investigated whether PLD is involved in the platelet activation of human...

Descripción completa

Detalles Bibliográficos
Autores principales: Lu, Wan Jung, Chung, Chi Li, Chen, Ray Jade, Huang, Li Ting, Lien, Li Ming, Chang, Chao Chien, Lin, Kuan Hung, Sheu, Joen Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262437/
https://www.ncbi.nlm.nih.gov/pubmed/30441821
http://dx.doi.org/10.3390/jcm7110440
_version_ 1783375105984823296
author Lu, Wan Jung
Chung, Chi Li
Chen, Ray Jade
Huang, Li Ting
Lien, Li Ming
Chang, Chao Chien
Lin, Kuan Hung
Sheu, Joen Rong
author_facet Lu, Wan Jung
Chung, Chi Li
Chen, Ray Jade
Huang, Li Ting
Lien, Li Ming
Chang, Chao Chien
Lin, Kuan Hung
Sheu, Joen Rong
author_sort Lu, Wan Jung
collection PubMed
description Phospholipase D (PLD) is involved in many biological processes. PLD1 plays a crucial role in regulating the platelet activity of mice; however, the role of PLD in the platelet activation of humans remains unclear. Therefore, we investigated whether PLD is involved in the platelet activation of humans. Our data revealed that inhibition of PLD1 or PLD2 using pharmacological inhibitors effectively inhibits platelet aggregation in humans. However, previous studies have showed that PLD1 or PLD2 deletion did not affect mouse platelet aggregation in vitro, whereas only PLD1 deletion inhibited thrombus formation in vivo. Intriguingly, our data also showed that the pharmacological inhibition of PLD1 or PLD2 does not affect mouse platelet aggregation in vitro, whereas the inhibition of only PLD1 delayed thrombus formation in vivo. These findings indicate that PLD may play differential roles in humans and mice. In humans, PLD inhibition attenuates platelet activation, adhesion, spreading, and clot retraction. For the first time, we demonstrated that PLD1 and PLD2 are essential for platelet activation in humans, and PLD plays different roles in platelet function in humans and mice. Our findings also indicate that targeting PLD may provide a safe and alternative therapeutic approach for preventing thromboembolic disorders.
format Online
Article
Text
id pubmed-6262437
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-62624372018-12-03 An Antithrombotic Strategy by Targeting Phospholipase D in Human Platelets Lu, Wan Jung Chung, Chi Li Chen, Ray Jade Huang, Li Ting Lien, Li Ming Chang, Chao Chien Lin, Kuan Hung Sheu, Joen Rong J Clin Med Article Phospholipase D (PLD) is involved in many biological processes. PLD1 plays a crucial role in regulating the platelet activity of mice; however, the role of PLD in the platelet activation of humans remains unclear. Therefore, we investigated whether PLD is involved in the platelet activation of humans. Our data revealed that inhibition of PLD1 or PLD2 using pharmacological inhibitors effectively inhibits platelet aggregation in humans. However, previous studies have showed that PLD1 or PLD2 deletion did not affect mouse platelet aggregation in vitro, whereas only PLD1 deletion inhibited thrombus formation in vivo. Intriguingly, our data also showed that the pharmacological inhibition of PLD1 or PLD2 does not affect mouse platelet aggregation in vitro, whereas the inhibition of only PLD1 delayed thrombus formation in vivo. These findings indicate that PLD may play differential roles in humans and mice. In humans, PLD inhibition attenuates platelet activation, adhesion, spreading, and clot retraction. For the first time, we demonstrated that PLD1 and PLD2 are essential for platelet activation in humans, and PLD plays different roles in platelet function in humans and mice. Our findings also indicate that targeting PLD may provide a safe and alternative therapeutic approach for preventing thromboembolic disorders. MDPI 2018-11-14 /pmc/articles/PMC6262437/ /pubmed/30441821 http://dx.doi.org/10.3390/jcm7110440 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lu, Wan Jung
Chung, Chi Li
Chen, Ray Jade
Huang, Li Ting
Lien, Li Ming
Chang, Chao Chien
Lin, Kuan Hung
Sheu, Joen Rong
An Antithrombotic Strategy by Targeting Phospholipase D in Human Platelets
title An Antithrombotic Strategy by Targeting Phospholipase D in Human Platelets
title_full An Antithrombotic Strategy by Targeting Phospholipase D in Human Platelets
title_fullStr An Antithrombotic Strategy by Targeting Phospholipase D in Human Platelets
title_full_unstemmed An Antithrombotic Strategy by Targeting Phospholipase D in Human Platelets
title_short An Antithrombotic Strategy by Targeting Phospholipase D in Human Platelets
title_sort antithrombotic strategy by targeting phospholipase d in human platelets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262437/
https://www.ncbi.nlm.nih.gov/pubmed/30441821
http://dx.doi.org/10.3390/jcm7110440
work_keys_str_mv AT luwanjung anantithromboticstrategybytargetingphospholipasedinhumanplatelets
AT chungchili anantithromboticstrategybytargetingphospholipasedinhumanplatelets
AT chenrayjade anantithromboticstrategybytargetingphospholipasedinhumanplatelets
AT huangliting anantithromboticstrategybytargetingphospholipasedinhumanplatelets
AT lienliming anantithromboticstrategybytargetingphospholipasedinhumanplatelets
AT changchaochien anantithromboticstrategybytargetingphospholipasedinhumanplatelets
AT linkuanhung anantithromboticstrategybytargetingphospholipasedinhumanplatelets
AT sheujoenrong anantithromboticstrategybytargetingphospholipasedinhumanplatelets
AT luwanjung antithromboticstrategybytargetingphospholipasedinhumanplatelets
AT chungchili antithromboticstrategybytargetingphospholipasedinhumanplatelets
AT chenrayjade antithromboticstrategybytargetingphospholipasedinhumanplatelets
AT huangliting antithromboticstrategybytargetingphospholipasedinhumanplatelets
AT lienliming antithromboticstrategybytargetingphospholipasedinhumanplatelets
AT changchaochien antithromboticstrategybytargetingphospholipasedinhumanplatelets
AT linkuanhung antithromboticstrategybytargetingphospholipasedinhumanplatelets
AT sheujoenrong antithromboticstrategybytargetingphospholipasedinhumanplatelets