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Open AccessArticle

Phospholipase D1 and D2 Synergistically Regulate Thrombus Formation

1
Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
2
Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan
3
Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
4
Department of Medical Research, Taipei Medical University Hospital, Taipei 110, Taiwan
5
Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 110, Taiwan
6
Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
7
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
8
Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan
9
Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, 110 Taipei, Taiwan
10
Institute of Biomedical Sciences, MacKay Medical College, New Taipei City 252, Taiwan
*
Authors to whom correspondence should be addressed.
The authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(18), 6954; https://doi.org/10.3390/ijms21186954
Received: 18 August 2020 / Revised: 17 September 2020 / Accepted: 20 September 2020 / Published: 22 September 2020
(This article belongs to the Special Issue Physiology of Platelets in Humans and Animals)
Previously, we reported that phospholipase D1 (PLD1) and PLD2 inhibition by selective PLD1 and PLD2 inhibitors could prevent platelet aggregation in humans, but not in mice. Moreover, only the PLD1 inhibitor, but not PLD2 inhibitor, could effectively prevent thrombus formation in mice, indicating that PLD might play different roles in platelet function in humans and mice. Although PLD1 and PLD2 were reported to be implicated in thrombotic events, the role of PLD in mice remains not completely clear. Here, we investigated the role of PLD1 and PLD2 in acute pulmonary thrombosis and transient middle cerebral artery occlusion-induced brain injury in mice. The data revealed that inhibition of PLD1, but not of PLD2, could partially prevent pulmonary thrombosis-induced death. Moreover, concurrent PLD1 and PLD2 inhibition could considerably increase survival rate. Likewise, inhibition of PLD1, but not PLD2, partially improved ischemic stroke and concurrent inhibition of PLD1, and PLD2 exhibited a relatively better protection against ischemic stroke, as evidenced by the infarct size, brain edema, modified neurological severity score, rotarod test, and the open field test. In conclusion, PLD1 might play a more important role than PLD2, and both PLD1 and PLD2 could act synergistically or have partially redundant functions in regulating thrombosis-relevant events. View Full-Text
Keywords: phospholipase D; platelet; thrombosis; middle cerebral artery occlusion phospholipase D; platelet; thrombosis; middle cerebral artery occlusion
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MDPI and ACS Style

Lien, L.-M.; Lu, W.-J.; Chen, T.-Y.; Lee, T.-Y.; Wang, H.-H.; Peng, H.-Y.; Chen, R.-J.; Lin, K.-H. Phospholipase D1 and D2 Synergistically Regulate Thrombus Formation. Int. J. Mol. Sci. 2020, 21, 6954. https://doi.org/10.3390/ijms21186954

AMA Style

Lien L-M, Lu W-J, Chen T-Y, Lee T-Y, Wang H-H, Peng H-Y, Chen R-J, Lin K-H. Phospholipase D1 and D2 Synergistically Regulate Thrombus Formation. International Journal of Molecular Sciences. 2020; 21(18):6954. https://doi.org/10.3390/ijms21186954

Chicago/Turabian Style

Lien, Li-Ming; Lu, Wan-Jung; Chen, Ting-Yu; Lee, Tzu-Yin; Wang, Hsueh-Hsiao; Peng, Hsien-Yu; Chen, Ray-Jade; Lin, Kuan-Hung. 2020. "Phospholipase D1 and D2 Synergistically Regulate Thrombus Formation" Int. J. Mol. Sci. 21, no. 18: 6954. https://doi.org/10.3390/ijms21186954

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