Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway

XueShuanTong (XST) comprising therapeutically active ginsenosides, a lyophilized extract of Panax notoginseng roots, is extensively used in traditional Chinese medicine to treat ischemic heart and cerebrovascular diseases. Our recent study shows that treatment with XST inhibits shear-induced thrombo...

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Main Authors: Lei Liu, Qiongling Zhang, Shunli Xiao, Zhengxiao Sun, Shilan Ding, Ying Chen, Lan Wang, Xiaojie Yin, Fulong Liao, Lin-Hua Jiang, Mei Xue, Yun You
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-03-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.606245/full
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spelling doaj-e939b48e368240338dde7109aa1677582021-03-22T05:49:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-03-011210.3389/fphar.2021.606245606245Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling PathwayLei Liu0Qiongling Zhang1Shunli Xiao2Zhengxiao Sun3Shilan Ding4Ying Chen5Lan Wang6Xiaojie Yin7Fulong Liao8Lin-Hua Jiang9Lin-Hua Jiang10Mei Xue11Yun You12Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaSino-UK Joint Laboratory of Brain Function and Injury, Xinxiang Medical University, Xinxiang, ChinaSchool of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomXiYuan Hosipital, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaXueShuanTong (XST) comprising therapeutically active ginsenosides, a lyophilized extract of Panax notoginseng roots, is extensively used in traditional Chinese medicine to treat ischemic heart and cerebrovascular diseases. Our recent study shows that treatment with XST inhibits shear-induced thrombosis formation but the underlying mechanism remained unclear. This study aimed to investigate the hypothesis that XST inhibited shear-induced platelet aggregation via targeting the mechanosensitive Ca2+-permeable Piezo1 channel by performing platelet aggregation assay, Ca2+ imaging and Western blotting analysis. Exposure to shear at physiologically (1,000–2000 s−1) and pathologically related rates (4,000–6,000 s−1) induced platelet aggregation that was inhibited by treatment with GsMTx-4. Exposure to shear evoked robust Ca2+ responses in platelets that were inhibited by treatment with GsMTx-4 and conversely enhanced by treatment with Yoda1. Treatment with XST at a clinically relevant concentration (0.15 g L−1) potently inhibited shear-induced Ca2+ responses and platelet aggregation, without altering vWF-mediated platelet adhesion and rolling. Exposure to shear, while resulting in no effect on the calpain-2 expression in platelets, induced calpain-2-mediated cleavage of talin1 protein, which is known to be critical for platelet activation. Shear-induced activation of calpain-2 and cleavage of talin1 were attenuated by treatment with XST. Taken together, our results suggest that XST inhibits shear-induced platelet aggregation via targeting the Piezo1 channel to prevent Piezo1-mediated Ca2+ signaling and downstream calpain-2 and talin1 signal pathway, thus providing novel insights into the mechanism of the therapeutic action of XST on platelet aggregation and thrombosis formation.https://www.frontiersin.org/articles/10.3389/fphar.2021.606245/fullxueshuantongshearplatelet aggregationpiezo1 channelCa2+
collection DOAJ
language English
format Article
sources DOAJ
author Lei Liu
Qiongling Zhang
Shunli Xiao
Zhengxiao Sun
Shilan Ding
Ying Chen
Lan Wang
Xiaojie Yin
Fulong Liao
Lin-Hua Jiang
Lin-Hua Jiang
Mei Xue
Yun You
spellingShingle Lei Liu
Qiongling Zhang
Shunli Xiao
Zhengxiao Sun
Shilan Ding
Ying Chen
Lan Wang
Xiaojie Yin
Fulong Liao
Lin-Hua Jiang
Lin-Hua Jiang
Mei Xue
Yun You
Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway
Frontiers in Pharmacology
xueshuantong
shear
platelet aggregation
piezo1 channel
Ca2+
author_facet Lei Liu
Qiongling Zhang
Shunli Xiao
Zhengxiao Sun
Shilan Ding
Ying Chen
Lan Wang
Xiaojie Yin
Fulong Liao
Lin-Hua Jiang
Lin-Hua Jiang
Mei Xue
Yun You
author_sort Lei Liu
title Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway
title_short Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway
title_full Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway
title_fullStr Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway
title_full_unstemmed Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway
title_sort inhibition of shear-induced platelet aggregation by xueshuantong via targeting piezo1 channel-mediated ca2+ signaling pathway
publisher Frontiers Media S.A.
series Frontiers in Pharmacology
issn 1663-9812
publishDate 2021-03-01
description XueShuanTong (XST) comprising therapeutically active ginsenosides, a lyophilized extract of Panax notoginseng roots, is extensively used in traditional Chinese medicine to treat ischemic heart and cerebrovascular diseases. Our recent study shows that treatment with XST inhibits shear-induced thrombosis formation but the underlying mechanism remained unclear. This study aimed to investigate the hypothesis that XST inhibited shear-induced platelet aggregation via targeting the mechanosensitive Ca2+-permeable Piezo1 channel by performing platelet aggregation assay, Ca2+ imaging and Western blotting analysis. Exposure to shear at physiologically (1,000–2000 s−1) and pathologically related rates (4,000–6,000 s−1) induced platelet aggregation that was inhibited by treatment with GsMTx-4. Exposure to shear evoked robust Ca2+ responses in platelets that were inhibited by treatment with GsMTx-4 and conversely enhanced by treatment with Yoda1. Treatment with XST at a clinically relevant concentration (0.15 g L−1) potently inhibited shear-induced Ca2+ responses and platelet aggregation, without altering vWF-mediated platelet adhesion and rolling. Exposure to shear, while resulting in no effect on the calpain-2 expression in platelets, induced calpain-2-mediated cleavage of talin1 protein, which is known to be critical for platelet activation. Shear-induced activation of calpain-2 and cleavage of talin1 were attenuated by treatment with XST. Taken together, our results suggest that XST inhibits shear-induced platelet aggregation via targeting the Piezo1 channel to prevent Piezo1-mediated Ca2+ signaling and downstream calpain-2 and talin1 signal pathway, thus providing novel insights into the mechanism of the therapeutic action of XST on platelet aggregation and thrombosis formation.
topic xueshuantong
shear
platelet aggregation
piezo1 channel
Ca2+
url https://www.frontiersin.org/articles/10.3389/fphar.2021.606245/full
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