Burgos C F, Méndez D, Quintana S, Gonkowski S, Trostchansky A, Alarcón M
Department of Physiology, Faculty of Biological Sciences, Universidad de Concepción, Concepción, Chile.
Thrombosis Research Center and Healthy Aging, Universidad de Talca, Talca, Chile.
Front Pharmacol. 2025 Apr 30;16:1526374. doi: 10.3389/fphar.2025.1526374. eCollection 2025.
Since the mid-20th century, the widespread use of plastics has led to the buildup of harmful byproducts in the environment-most notably acrylamide (AA) and bisphenol A (BPA). These chemicals are now commonly detected in human tissues, raising concerns about their potential health effects. While their presence as environmental pollutants is well known, their specific impact on platelet function and the associated cardiovascular risks remains poorly understood.
To explore how AA and BPA affect platelet physiology, we performed in vitro assays to assess platelet activation and aggregation following exposure to these compounds. We also used bioinformatic tools to identify potential protein targets in human platelets and carried out molecular docking simulations to investigate how AA and BPA interact with key enzymes involved in platelet regulation.
Both AA and BPA exposure led to a significant increase in platelet activation and aggregation, suggesting an elevated risk of thrombosis. Proteomic analysis identified around 1,230 potential protein targets, with 191 affected by AA and 429 by BPA. These proteins are primarily involved in oxidative stress, apoptosis, and signaling pathways regulated by protein kinase C (PKC), p38α-MAPK, and superoxide dismutase (SOD). Molecular modeling further revealed that AA and BPA form stable complexes with several of these enzymes, indicating direct interference with platelet function.
Our study shows that AA and BPA can enhance platelet reactivity and aggregation, which are key factors in the development of cardiovascular disease (CVD). By identifying specific molecular pathways and targets affected by these pollutants, we provide new insights into their potential role in promoting thrombotic conditions. These findings highlight the urgent need for greater public health awareness and stronger regulatory efforts to reduce human exposure to AA and BPA.
自20世纪中叶以来,塑料的广泛使用导致环境中有害副产物的积累——最显著的是丙烯酰胺(AA)和双酚A(BPA)。现在在人体组织中普遍检测到这些化学物质,这引发了人们对其潜在健康影响的担忧。虽然它们作为环境污染物的存在是众所周知的,但它们对血小板功能和相关心血管风险的具体影响仍知之甚少。
为了探究AA和BPA如何影响血小板生理功能,我们进行了体外试验,以评估暴露于这些化合物后血小板的活化和聚集情况。我们还使用生物信息学工具来识别人类血小板中的潜在蛋白质靶点,并进行分子对接模拟,以研究AA和BPA如何与参与血小板调节的关键酶相互作用。
暴露于AA和BPA均导致血小板活化和聚集显著增加,这表明血栓形成风险升高。蛋白质组学分析确定了约1230个潜在蛋白质靶点,其中191个受AA影响,429个受BPA影响。这些蛋白质主要参与氧化应激、细胞凋亡以及由蛋白激酶C(PKC)、p38α-丝裂原活化蛋白激酶(MAPK)和超氧化物歧化酶(SOD)调节的信号通路。分子建模进一步表明,AA和BPA与其中几种酶形成稳定的复合物,表明它们直接干扰血小板功能。
我们的研究表明,AA和BPA可增强血小板反应性和聚集,而这是心血管疾病(CVD)发生发展的关键因素。通过识别受这些污染物影响的特定分子途径和靶点,我们为它们在促进血栓形成状况中的潜在作用提供了新的见解。这些发现凸显了迫切需要提高公众健康意识并加强监管力度,以减少人类接触AA和BPA。