The role of platelets in hemostasis and thrombosis has long been recognized, recently their contribution to immunological and inflammatory processes is emerging. Platelets could be the missing link between cardiovascular disease, chronic stress and depressive symptoms. Both physical and mental stressors cause platelet activation reflected by changes in platelet bioactivity and aggregation. Here we evaluate the proinflammatory platelet response to acute and chronic mental stress. In a prospective study design an acute mental stress test was administered to 55 healthy male participants once without and once in the presence of chronic mental stress. Blood was collected prior to and at three time points following an acute mental stress test (0, 30, 60 min). Platelet proinflammatory activation markers, were assessed using FACS analysis and aggregability was measured in response to ADP or epinephrine using PFA-100. A linear mixed model was used for analysis. Chronic mental stress lead to a significant increase in state anxiety (p < 0.001), depressive symptoms (p = 0.045) and perceived stress (p = 0.001). The factor “chronic mental stress” was significantly associated with increased numbers of CD63+ platelets (p = 0.009). The factor “acute mental stress” was associated with alterations in CD62P+ platelets (p < 0.001), CD63+ platelets (p = 0.011), PAC-1+ platelets (p < 0.001) as well as platelet leucocyte aggregates (p = 0.019). The recovery of CD62P function following the acute mental stress exposure was significantly impaired by chronic stress (p = 0.023). Aggregation was affected by chronic and acute mental stress. In conclusion, mental stress is linked to an increased and prolonged proinflammatory platelet bioactivity. This proinflammatory and immunomodulatory stimuli could help to explain the link between mental and somatic disorders.

Graphical Abstract

血小板在止血和血栓形成中的作用早已得到认可，最近它们对免疫和炎症过程的贡献正在显现。血小板可能是心血管疾病、慢性压力和抑郁症状之间缺失的环节。身体和精神压力因素都会导致血小板活化，这反映在血小板生物活性和聚集的变化上。在这里，我们评估了对急性和慢性精神压力的促炎血小板反应。在一项前瞻性研究设计中，对 55 名健康男性参与者进行了一次急性精神压力测试，一次没有慢性精神压力，一次存在慢性精神压力。在急性精神压力测试之前和之后的三个时间点（0、30、60 分钟）收集血液。血小板促炎激活标志物，使用 FACS 分析进行评估，并使用 PFA-100 测量响应于 ADP 或肾上腺素的聚集性。使用线性混合模型进行分析。慢性精神压力导致状态焦虑显着增加（p  < 0.001)、抑郁症状 ( p  = 0.045) 和感知压力 ( p  = 0.001)。“慢性精神压力”因素与 CD63+ 血小板数量的增加显着相关 ( p  = 0.009)。“急性精神压力”因素与 CD62P+ 血小板 ( p  < 0.001)、CD63+ 血小板 ( p  = 0.011)、PAC-1+ 血小板 (p < 0.001) 以及血小板白细胞聚集 ( p  = 0.019) 的改变有关。慢性应激显着损害急性精神应激暴露后 CD62P 功能的恢复（p = 0.023）。聚集受到慢性和急性精神压力的影响。总之，精神压力与促炎血小板生物活性的增加和延长有关。这种促炎和免疫调节刺激有助于解释精神障碍和躯体障碍之间的联系。

图形概要