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Article

An Antithrombotic Strategy by Targeting Phospholipase D in Human Platelets

1
Department of Medical Research, Taipei Medical University Hospital, Taipei 110, Taiwan
2
Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
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Graduate Institute of Metabolism and Obesity Sciences, College of Public Health and Nutrition, Taipei Medical University, Taipei 110, Taiwan
4
Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan
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School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
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Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei 110, Taiwan
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School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
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Department of Neurology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan
9
Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan
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Institute of Biomedical Sciences, Mackay Medical College, New Taipei City 252, Taiwan
11
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
*
Authors to whom correspondence should be addressed.
Received: 12 October 2018 / Revised: 6 November 2018 / Accepted: 13 November 2018 / Published: 14 November 2018
(This article belongs to the Section Vascular Medicine)
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. View Full-Text
Keywords: phospholipase D; platelet activation; clot retraction; thrombus formation phospholipase D; platelet activation; clot retraction; thrombus formation
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MDPI and ACS Style

Lu, W.J.; Chung, C.L.; Chen, R.J.; Huang, L.T.; Lien, L.M.; Chang, C.C.; Lin, K.H.; Sheu, J.R. An Antithrombotic Strategy by Targeting Phospholipase D in Human Platelets. J. Clin. Med. 2018, 7, 440. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm7110440

AMA Style

Lu WJ, Chung CL, Chen RJ, Huang LT, Lien LM, Chang CC, Lin KH, Sheu JR. An Antithrombotic Strategy by Targeting Phospholipase D in Human Platelets. Journal of Clinical Medicine. 2018; 7(11):440. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm7110440

Chicago/Turabian Style

Lu, Wan J., Chi L. Chung, Ray J. Chen, Li T. Huang, Li M. Lien, Chao C. Chang, Kuan H. Lin, and Joen R. Sheu 2018. "An Antithrombotic Strategy by Targeting Phospholipase D in Human Platelets" Journal of Clinical Medicine 7, no. 11: 440. https://0-doi-org.brum.beds.ac.uk/10.3390/jcm7110440

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