Polymer-specific nanoplastic exposure, mitochondrial dysfunction, and depressed ejection fraction in humans
Alberta Maria Maddalena Palazzo, Lucia Scisciola, Manuela Giovanna Basilicata, Nunzia D’Onofrio, Pasquale Paolisso, Angelo Fenti, Francesco Prattichizzo, Celestino Sardu, Eduardo Sommella, Valentina Golino, Marta Belmonte, Asad Zia, Claudio Marra, Cristiano Amarelli, Laura Graciotti, Gianluca Fulgenzi, Fabiola Olivieri, Rosalba La Grotta, Antonio Ceriello, Maria Luisa Balestrieri, Bruno D’Agostino, Carmine Lubritto, Pasquale Iovino, Claudio Napoli, Pietro Campiglia, Emanuele Barbato, Philip Landrigan, Michelangela Barbieri, Raffaele Marfella, Giuseppe PaolissoAbstract
Aims
Micro- and nanoplastics (MNPs) are increasingly found in humans, but cardiac and energetic effects are unclear.
Methods and Results
In older adults without major comorbidities, blood levels of PS/PE were quantified, and left ventricular ejection fraction (EF) was measured by transthoracic echocardiography. To investigate polymer-specific cardiotoxic mechanisms, human AC16 cardiomyocytes were exposed to PS- or PE-nanoplastics. Mitochondrial function was assessed using Seahorse XF analysis, and molecular remodeling was characterized using transcriptomics and label-free quantitative proteomics.
In humans, circulating PS and PE levels were each associated with EF in univariable analyses. PS and PE concentrations were higher in participants with EF <50% than in those with EF ≥50% (PE p=0.021; PS p<0.001). After multivariable adjustment for anthropometric and metabolic determinants of systolic function, PS remained independently associated with EF. In vitro, both polymers accumulated intracellularly and elicited mitochondrial stress. Chronic PS exposure induced a loss of respiratory capacity and bioenergetic reserve, with suppression of basal and maximal respiration and markedly reduced spare respiratory capacity. PE exposure produced a distinct remodeling pattern characterized by reduced maximal respiration, but increased ATP-linked respiration and tighter respiratory coupling, consistent with a compensatory state of reduced metabolic flexibility. Transcriptomic profiling revealed polymer-specific transcriptional phenotypes, with PE driving broader repression of cardiomyocyte structural, electrophysiological, and mitochondrial gene programs, whereas PS triggered a more restricted but coherent response. Proteomic profiling further identified a mitochondria-centered injury signature involving disruption of mitochondrial protein import and cristae organization, impairment of oxidative metabolism, altered redox buffering, and incomplete activation of mitochondrial quality-control pathways.
Conclusions
Nanoplastic exposure is associated with left ventricular systolic function in humans and induces polymer-specific cardiomyocyte remodeling in vitro. PS is strongly linked to systolic impairment, consistent with a mitochondria-centered cardiotoxic phenotype. These findings identify nanoplastics as a previously unrecognized environmental determinant of myocardial vulnerability and support polymer-specific risk stratification.