Heatwave increases the risk of ischemic stroke by promoting platelet activation

With global warming and an aging population, the risk of cerebrovascular disease caused by environmental heat exposure increases.

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.

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.

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.

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.