Heatwave increases the risk of ischemic stroke by promoting platelet activation

Résumé fourni par la source

BACKGROUND: With global warming and an aging population, the risk of cerebrovascular disease caused by environmental heat exposure increases. OBJECTIVE: Given the critical role of platelet activation and thrombosis in ischemic stroke, this study aimed to investigate the effects and underlying biological mechanisms of heatwaves on platelet activation. METHODS: During the hot season (May to September) from 2018 to 2020, 1830 patients with acute ischemic stroke admitted to four stroke centers in Tianjin were enrolled. ADP-induced platelet aggregation, platelet parameters, and other markers of platelet activation were compared during heatwave and non-heatwave periods. Then, platelet function was evaluated in heatwave-exposed mice (39 ± 1℃ for 8 h/22℃ for 16 h, 3d) and normal temperature-exposed mice (22℃, 24 h, 3d). In addition, washed platelets were subjected to heat stress treatment and agonist induction to detect phosphorylation of HSF1 and screen for target inhibitors. RESULTS: The ADP-induced platelet aggregation was significantly higher during heatwaves than during non-heatwaves (37.07 % vs 35.04 %, P = 0.02). Consistently, animal experiments also confirmed that heatwave exposure enhanced ADP, thrombin, and collagen induced platelet aggregation (5 μM ADP: 42.19 % vs 31.01 %; 0.02 U/mL thrombin:71.37 % vs 48.87 %, 1 µg/mL collagen: 62.65 % vs 30.73 %, P < 0.05). Furthermore, mice exposed to heatwaves had faster clot retraction speeds, shorter tail bleeding times, and larger mesenteric thrombosis volumes compared to normal temperature mice. Mechanism analysis found that platelet p-P38/p-AKT/p-HSF1 may be involved in heat stress-induced platelet activation, and HSF1 specific inhibitor DTHIB had anti-platelet effect. CONCLUSION: Exposure to heatwaves may promote platelet activation, and p-P38/p-AKT/p-HSF1 may be involved in this process. These results provide a basis for understanding the underlying mechanisms of heatwave-related cerebrovascular diseases.

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