Impact of Micro- and Nanoplastics on Heart Health and Disease

About This Grant

PROJECT SUMMARY Micro- and nanoplastics (MNPs) are emerging as a ubiquitous and persistent environmental contaminant. Human exposure to MNPs is widespread, with ingestion being the main exposure route. Research addressing the potential impact of MNPs on human health is urgently needed. MNPs can reach and accumulate in the heart. However, the impact of MNPs on the heart is very poorly understood. Notably, a recent epidemiologic study has shown that higher exposure to MNPs is associated with increased cardiovascular events in human patients. This new evidence highlights the potential cardiovascular toxicity of MNPs in humans and the critical need to understand the effects of MNPs exposure on the heart. In preliminary studies in human inducible pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and/or rats, we found that exposure to MNPs caused cardiac toxicity including reduced cardiac myocyte viability, increased reactive oxygen species (ROS), and decreased left ventricular mass. Remarkably, in rat exposure studies, we found that MPNs exposure significantly increased myocardial infarction size and cardiac tissue damage following cardiac ischemia injury. Supported by compelling preliminary results, we propose to address the central hypothesis that exposure to environmental MNPs causes mitochondrial dysfunction and oxidative stress in the heart, leading to increased susceptibility of the heart to damage; such cardiac toxicity is manifested as worsened infarction and heart dysfunction following ischemia injury (ie, heart attack). The proposed study will be carried out by an interdisciplinary team that comprises researchers in cardiac toxicology, chemistry, clinical cardiology, and biostatistics. The study uses both an in vivo rat model and human iPSC-derived cardiomyocytes and human cardiac organoid models, and are of strong relevance to human heart health. Importantly, taking advantage of our breakthroughs in producing “true-to-life” MNPs that mimic real-life environmental MNPs, we will use such “true-to-life” MNPs in the entire study, making the study highly relevant to real-life environmental MNPs exposure. In whole animal exposure studies, internal MNPs exposure levels and tissue distribution will be analyzed using state-of-the-art analytical chemistry approaches. Three aims are proposed. Aim 1 examines the impact of MNPs on cardiac physiology and function; Aim 2 addresses the impact of MNPs on cardiac damage and adverse outcomes following ischemia injury; Aim 3 examines the mechanism underlying MNPs-induced cardiac toxicity, focusing on the autophagy-lysosome pathway and mitochondria dysfunction. The proposed studies are significant because they are expected to provide critical knowledge on MNPs-induced cardiac toxicity in human-relevant experimental models, thus having strong environmental health significance. Further, the studies will contribute to our recognition of the role of MNPs in affecting the outcomes of heart attack - a top cause of death and morbidity in the US, thus having strong clinical and translational impact.