Cardiac Effects of Weathered Microplastics - PROJECT SUMMARY Microplastics (MPs) are increasingly detected in human tissues, including the heart. An observational study has linked their presence to elevated risks of myocardial infarction, stroke, and death. Foundational work with pristine, uniform, spherical polystyrene (PS) has provided evidence that PS-MP can disrupt cardiomyocyte contractility, calcium handling, and electrophysiological stability at environmentally relevant concentrations. However, the spherical pristine PS-MP particles do not reflect what humans encounter in the real world. Environmental MPs represent a highly varied class of pollutants, encompassing a wide range of physical and chemical characteristics, including, but not limited to, size, shape, polymer type, chemical additives, absorbed chemicals, and aging/weathering status. The MPs to which humans are exposed in the real world are primarily weathered, resulting from their exposure to ultraviolet (UV) radiation, heat, hydrolysis, mechanical abrasion, and interactions with other environmental chemicals. The weathering process alters the physicochemical properties of MPs, including surface oxidation, fragmentation, increased roughness, and stronger adsorption – features that can fundamentally alter MP toxicity. Given that all real-world MPs are inevitably weathered in the natural environments, a crucial knowledge gap exists: are weathered MPs more harmful to human health? The goal of this project is to test the central hypothesis that environmentally realistic weathered MPs induce distinct, and potentially more harmful, biological effects on mammalian hearts than pristine MPs. We will align in vitro, ex vivo, and in vivo systems to ensure rigorous translational relevance. In Aim 1, human iPSC-derived cardiomyocytes (hiPSC-CMs) and isolated adult mouse cardiomyocytes will be exposed to pristine versus weathered MPs; we will quantify particle uptake, measure contractility and Ca²⁺ transients, and map perturbed pathways by RNA-seq and targeted protein assays, with a focus on calcium handling, adrenergic signaling, lipid metabolism, and estrogen signaling. In Aim 2, mice will undergo chronic oral exposure to pristine versus weathered MPs. We will evaluate the cardiac consequences of ingesting MPs and the systemic pathways mediating injury by conducting cardiomyocyte contractility assays and Langendorff-perfused isolated heart studies under both physiological and pathological conditions, as well as analyzing metabolic, inflammatory, and biological sex-specific effects. This work will expand the institutional research capacity in cardiotoxicity and environmental health, establish scalable platforms for testing complex MP pollutants, and provide hands-on training for undergraduate and graduate students in translational environmental health research.
