微塑料颗粒（MP）在工业生产和自然环境中普遍存在，对人类健康构成重大关切。日常饮食、吸入空气和皮肤接触是人类摄入MP的主要方式。MP对人体的主要伤害靶系统包括消化系统、呼吸系统和心血管系统。然而，关于MP对心脏的不良影响的研究相对较少。以往的体内研究已经证明，MP可以引发心脏损伤，包括心律异常、心肌细胞凋亡、线粒体膜电位改变和纤维蛋白过度表达。为了解决动物福利问题和克服物种间差异，本研究采用人类多能干细胞衍生的体外三维心脏器官样结构（CO）模型，研究MP对人心脏的不良影响。CO的明显腔体结构使得可以观察到经过聚苯乙烯微塑料（PS-MP）暴露后的MP的聚集和空间分布情况。在暴露于不同浓度的PS（0.025、0.25和2.5 µg/mL，最低浓度相当于人类内部暴露水平）后，CO显示出增加的氧化应激、炎症反应、细胞凋亡和胶原蛋白积累。这些发现与体内观察结果一致，包括室间隔厚度的增加。CO的肥大相关基因表达（MYH7B/ANP/BNP/COL1A1）明显改变，心脏特异性标记物MYL2/MYL4/CX43也显著升高。我们的发现揭示了PS可以在体内和体外引发心肌肥大，表明MP可能是心血管系统的一个未被认识的危险因素。版权所有©2023 The Author(s)。由Elsevier Ltd出版。保留所有权利。

Microplastic particles (MP) are prevalent in both industrial production and the natural environment, posing a significant concern for human health. Daily diet, air inhalation, and skin contact are major routines of MP intake in human. The main injury target systems of MPs include the digestive system, respiratory system, and cardiovascular system. However, the study on MPs' adverse effects on the heart is less than other target organs. Previous in vivo studies have demonstrated that MPs can induce heart injuries, including abnormal heart rate, apoptosis of cardiomyocytes, mitochondrial membrane potential change, and fibrin overexpression. To address animal welfare concerns and overcome inter-species variations, this study employed a human pluripotent stem cell-derived in vitro three-dimensional cardiac organoid (CO) model to investigate the adverse effects of MPs on the human heart. The distinct cavities of COs allowed for the observation of MPs' aggregation and spatial distribution following polystyrene-MP (PS) exposure in a dynamic exposure system. After exposure to various concentrations of PS (0.025, 0.25 and 2.5 µg/mL, with the lowest concentration equivalent to human internal exposure levels), the COs exhibited increased oxidative stress, inflammatory response, apoptosis, and collagen accumulation. These findings were consistent with in vivo observations, in terms of increases in the interventricular septal thickness. The expression of hypertrophic-related genes of COs (MYH7B/ANP/BNP/COL1A1) changed noticeably and the cardiac-specific markers MYL2/MYL4/CX43 were also markedly elevated. Our findings revealed the PS could induced cardiac hypertrophy in vivo and in vitro, indicating that MP may be an under-recognized risk factor for cardiovascular system.Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.