Journal
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume 19, Issue 12, Pages 3113-3125Publisher
WILEY
DOI: 10.1111/jth.15504
Keywords
hypertension; mitochondria; platelet; stroke; thrombosis
Categories
Funding
- National Major Scientific and Technological Special Project for Significant New Drugs Development [2019ZX09201005-005-001, 2019ZX09201005-005-004]
- National Natural Science Foundation of China [81673710, 81973580]
- Innovative Chinese Medicine and Health Products Research Academician Workstation of Academician Boli Zhang and Academician Beiwei Zhu, West China Hospital,Sichuan University [HXYS19001, HXYS19002]
- Sichuan Science and Technology Department Emergency Project for COVID-19 [2020YFS0554]
- Applied Basic Research Programs of Department of Science and Technology of Sichuan Province [2019YJ0095]
- National Science Foundation for Young Scientists of China [81803866]
- China Postdoctoral Science Foundation [2018M640932, 2019T120854]
- Post-Doctor Research Project, West China Hospital, Sichuan University [2018HXBH061, 2019HXBH024]
- Postdoctoral Interdisciplinary Research Project of Sichuan University [2019JCXK3245]
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The activation of mechanoreceptor Piezo1 under hypertension is crucial for abnormal platelet activation and thrombosis, while inhibition of Piezo1 can effectively prevent arterial thrombosis caused by hypertension.
Background Thrombosis is the pathological basis of cardiovascular and cerebrovascular diseases, which seriously threaten human life and health. Among them, nearly half of cardiovascular disease patients suffer from severe hypertension complications. Hypertension is thought to cause abnormal platelet activation and increases the risk of thrombosis, but the related mechanism is still vague. Objectives This study hypothesized that the abnormal hemodynamics of blood under hypertension might affect platelet function and accelerate thrombosis by activating mechanoreceptor Piezo1. Methods To assess the activation effect of hypertension on mechanoreceptor Piezo1, we injected Piezo1 agonist Yoda1 and antagonist GsMTx-4 through the tail vein, then examined the platelet activation status and thrombosis. Results Our results displayed that antagonist GsMTx-4 effectively inhibited calcium influx caused by hypertension and agonist Yoda1. Antithrombotic studies proved that the inhibition of Piezo1 effectively inhibited arterial thrombosis and reduced the infarct size of stroke in hypertensive mice. Conclusions Our study explains the activation of mechanoreceptor Piezo1 under hypertension is the key to abnormal platelet activation and thrombosis while providing novel platelet intervention strategies to prevent thrombosis.
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