Micro(nano)plastics in the Development of Myocardial Fibrosis: From Clinical Detection to Molecular Mechanism

Micro(nano)plastics (MNPs) are pervasive environmental contaminants, yet their presence in human cardiac tissue and their potential contribution to myocardial fibrosis remain unclear. We investigated whether myocardial MNP burden is associated with fibrosis severity in patients and evaluated mechanistic plausibility in mice.

Left atrial appendage tissues were collected from patients undergoing cardiac surgery (n=33). MNP burden and polymer composition were quantified by pyrolysis-gas chromatography/mass spectrometry, and fibrosis was quantified histologically. In mice, 100-nm or 1-µm polystyrene nanoplastics were administered by oral gavage in coexposure and sequential exposure protocols with isoprenaline. Cardiac function was assessed by echocardiography, and fibrosis was evaluated by histology and immunohistochemistry. Transcriptomics, metabolomics, and 16S ribosomal RNA sequencing were performed to identify pathways linked to MNP exposure.

MNPs were detected in all human cardiac samples. Patients with high fibrosis exhibited higher total MNP levels than those with low fibrosis (171.74 [interquartile range [IQR], 158.18-202.39] versus 119.33 [IQR, 102.75-148.44] µg/g tissue; P=2.5×10^-4), driven predominantly by elevated nanoplastics (122.83 [IQR, 100.10-149.06] versus 86.39 [IQR, 36.85-103.74] µg/g; P=0.010). Polystyrene and polyvinyl chloride were enriched in high-fibrosis tissues (polystyrene: P=3.3×10^-4; polyvinyl chloride: P=0.002). Transcriptomics indicated activation of inflammatory and profibrotic pathways (TNF [tumor necrosis factor]/NF-κB [nuclear factor-κB], TGF-β [transforming growth factor-beta], and MAPK [mitogen-activated protein kinase]), supported by increased α-SMA (alpha-smooth muscle actin), COL1 (collagen I), and TGF-β1 immunostaining, while metabolomics suggested perturbations in lipid metabolism and mitochondrial function. In mice, polystyrene exposure exacerbated isoprenaline-induced systolic dysfunction and myocardial fibrosis in both experimental paradigms and recapitulated pathway signatures related to cell-matrix interactions.

Myocardial MNP burden, particularly nanoplastics, is associated with greater fibrosis in humans, and experimental polystyrene exposure aggravates stress-induced myocardial remodeling in vivo. Multiomics analyses nominate inflammatory, ECM (extracellular matrix), and metabolic programs as candidate mediators of MNP-associated cardiotoxicity.