Abstract：
Nanoplastics (NPs) pollution has become a global environmental problem, raising numerous health concerns. However, the cardiotoxicity of NPs exposure and the underlying mechanisms have been understudied to date. To address this issue, we comprehensively evaluated the cardiotoxicity of polystyrene nanoplastics (PS-NPs) in both healthy and pathological states. Briefly, mice were orally exposed to four different concentrations (0 mg/day, 0.1 mg/day, 0.5 mg/day, and 2.5 mg/day) of 100-nm PS-NPs for 6 weeks to assess their cardiotoxicity in a healthy state. Considering that individuals with underlying health conditions are more vulnerable to the adverse effects of pollution, we further investigated the cardiotoxic effects of PS-NPs on pathological states induced by isoprenaline. Results showed that PS-NPs induced cardiomyocyte apoptosis, cardiac fibrosis, and myocardial dysfunction in healthy mice and exacerbated cardiac remodeling in pathological states. RNA sequencing revealed that PS-NPs significantly upregulated homeodomain interacting protein kinase 2 (HIPK2) in the heart and activated the P53 and TGF-beta signaling pathways. Pharmacological inhibition of HIPK2 reduced P53 phosphorylation and inhibited the activation of the TGF-β1/Smad3 pathway, which in turn decreased PS-NPs-induced cardiotoxicity. This study elucidated the potential mechanisms underlying PS-NPs-induced cardiotoxicity and underscored the importance of evaluating nanoplastics safety, particularly for individuals with pre-existing heart conditions.
摘要：
纳米塑料(NPs)污染已成为全球性的环境问题,引发了许多健康问题。然而,NPs暴露的心脏毒性和潜在机制迄今尚未得到充分研究.为了解决这个问题，我们全面评估了聚苯乙烯纳米塑料（PS-NP）在健康和病理状态下的心脏毒性。简而言之，小鼠口服暴露于四种不同浓度(0毫克/天，0.1毫克/天，0.5毫克/天，和2.5mg/天）的100-nmPS-NP持续6周，以评估其在健康状态下的心脏毒性。考虑到具有潜在健康状况的个人更容易受到污染的不利影响，我们进一步研究了PS-NP对异丙肾上腺素诱导的病理状态的心脏毒性作用.结果显示PS-NPs诱导心肌细胞凋亡,心脏纤维化，健康小鼠的心肌功能障碍和病理状态下的心脏重塑加剧。RNA测序显示，PS-NP显着上调心脏中同源结构域相互作用蛋白激酶2（HIPK2），并激活P53和TGF-β信号通路。HIPK2的药理学抑制降低了P53磷酸化并抑制了TGF-β1/Smad3通路的激活,这反过来降低了PS-NP诱导的心脏毒性。这项研究阐明了PS-NP诱导心脏毒性的潜在机制，并强调了评估纳米塑料安全性的重要性。特别是对于预先存在心脏病的人。
