ESC Congress 2026 Abstract · Oct 26, 2026
Pharmacological inhibition of microplastic uptake prevents endothelial injury
By Tortorella G, Sanchez-Ceinos J, Fontanive G et al.
Background: Emerging evidence has turned strong attention to the possible harmful effects of micro- and nanoplastics (MNPs; <5 mm and <1 μm in diameter, respectively). They have been detected in human blood and in the vascular wall, raising concerns about their potential contribution to cardiovascular disease (CVD). Experimental evidence indicates that polystyrene (PS) induces endothelial dysfunction, but its cellular internalization pathways as well as the molecular mechanisms triggering endothelial injury remain unexplored. Purpose: To determine whether pharmacological inhibition of PS internalization may restore endothelial function. Methods: Human aortic endothelial cells (HAECs) and aortas isolated from wild-type mice were exposed to PS (size: 2 µm, 200μg/mL for 24 hours) with or without pretreatment with amiloride (20μM), an inhibitor of macropinocytosis. Intracellular uptake and localization were assessed by confocal and transmission electron microscopy. Oxidative stress, inflammatory signaling, nitric oxide availability and monocyte adhesion were quantified by molecular and functional assays. Vascular reactivity was assessed in isolated mouse thoracic aortic rings mounted in a wire myograph system. Human peripheral blood samples were obtained from 30 participants, well matched for several parameters (mean age 71.5 ± 12 years, systolic arterial pressure: 130 ± 14 mmHg, glucose: 5.2 ± 1.1 mmol/L, LDL: 100 ± 45 mg/dL, HDL: 52 ± 14 mg/dL, triglycerides: 116 ± 70 mg/dL). These peripheral blood samples were analyzed for PS content using pyrolysis–gas chromatography–mass spectrometry (Py-GC/MS). Flow-mediated dilation (FMD) of the brachial artery was performed in the same subjects. Results: Internalization and cytoplasmic localization of PS in HAECs induced upregulation of oxidative and inflammatory genes with subsequent increase in ROS production, reduced NO bioavailability and monocyte adhesion. Impaired endothelium-dependent relaxation was observed in mouse aortic rings exposed to PS. Circulating PS was detected in human blood samples. Higher PS levels were inversely associated with FMD, supporting a link between particle exposure and impaired endothelial function in humans. Pharmacological inhibition of PS uptake with amiloride in HAECs significantly reduced intracellular particle accumulation and attenuated oxidative and inflammatory signaling. This was accompanied by restoration of NO bioavailability, reduced monocyte adhesion, and marked improvement of endothelium-dependent vasodilation in exposed mouse aortic rings, supporting a causal role of intracellular particle internalization in mediating endothelial injury. Conclusions: Internalization of PS plays a central role in the onset of endothelial oxidative and inflammatory phenotypes, identifying a potential target to reduce the cardiovascular impact of environmental microplastic exposure.Graphical Abstract ESCFor image description, please refer to the figure legend and surrounding text.