Piezo1 initiates platelet hyperreactivity and accelerates thrombosis in hypertension.

ABSTRACT

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.