Low-dose of polystyrene microplastics induce cardiotoxicity in mice and human-originated cardiac organoids

Abstract

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.

Keywords: Cardiac hypertrophy; Cardiac organoid; Human embryonic stem cells; Microplastics.