TY - JOUR
T1 - Phospholipase D1 and D2 synergistically regulate thrombus formation
AU - Lien, Li Ming
AU - Lu, Wan Jung
AU - Chen, Ting Yu
AU - Lee, Tzu Yin
AU - Wang, Hsueh Hsiao
AU - Peng, Hsien Yu
AU - Chen, Ray Jade
AU - Lin, Kuan Hung
N1 - Funding Information:
Funding: This work was supported by grants from the Ministry of Science and Technology of Taiwan (MOST 105-2320-B-341-001, MOST 106-2320-B-715-006-MY3, MOST 109-2320-B-715-003-MY3, MOST 105-2311-B-038-005-MY3, MOST 108-2320-B-038-063, MOST 109-2320-B-038-044-MY3, MOST 108-2320-B-038-029, and MOST 109-2320-B-038-054), Taipei Medical University Hospital (107TMU-TMUH-14, 108TMU-TMUH-11, and 109TMUH-SP-01), MacKay Medical College (1071B13 and 1081A02), and Shin Kong Wu Ho-Su Memorial Hospital (2018SKHADR013 and 2019SKHADR017).
Funding Information:
This work was supported by grants from the Ministry of Science and Technology of Taiwan (MOST 105-2320-B-341-001, MOST 106-2320-B-715-006-MY3, MOST 109-2320-B-715-003-MY3, MOST 105-2311-B-038-005-MY3, MOST 108-2320-B-038-063, MOST 109-2320-B-038-044-MY3, MOST 108-2320-B-038-029, and MOST 109-2320-B-038-054), Taipei Medical University Hospital (107TMU-TMUH-14, 108TMU-TMUH-11, and 109TMUH-SP-01), MacKay Medical College (1071B13 and 1081A02), and Shin Kong Wu Ho-Su Memorial Hospital (2018SKHADR013 and 2019SKHADR017). Acknowledgments: The authors appreciate Chih-Hao Yang (Department of Pharmacology, Taipei Medical University, Taiwan) for supporting the animal experiments, respectively.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/9/2
Y1 - 2020/9/2
N2 - 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.
AB - 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.
KW - Middle cerebral artery occlusion
KW - Phospholipase D
KW - Platelet
KW - Thrombosis
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U2 - 10.3390/ijms21186954
DO - 10.3390/ijms21186954
M3 - Article
C2 - 32971863
AN - SCOPUS:85091277255
SN - 1661-6596
VL - 21
SP - 1
EP - 13
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 18
M1 - 6954
ER -