Microplastics (MPs) are emerging environmental contaminants that are increasingly detected in human tissues and are potentially linked to cardiovascular risk through oxidative and inflammatory mechanisms [1]. However, their impact on cardiac lipid signalling, a key regulator of cardiomyocyte function and cardiovascular homeostasis, remains largely unexplored.

This study investigated the time-dependent effects of virgin and artificially aged MPs (4 weeks, photodegradation at 40 °C and 750 W/m²) [2] on oxylipin profiles in cardiomyocytes, with a focus on the arachidonic acid (AA) cascade. Human induced-pluripotent stem cells cardiomyocytes (hiPSC-CMs) were exposed to a panel of well-characterized MPs, polystyrene (PS), high- and low-density polyethylene (HDPE, LDPE), polyethylene terephthalate (PET), and polypropylene (PP) [3]. Cell viability, oxidative stress (H2O2 production), inflammasome (Caspase-1), and inflammation (IL-6, TNF-alpha) were quantified using different assays at day 7. Oxylipins in culture media were quantified using a validated UHPLC–MS/MS platform [4] after 2, 4, and 7 days of exposure.

Cell viability results showed a significant reduction in aged LDPE. Oxidative stress was higher in virgin HDPE, PS, and LDPE (virgin and aged). Caspase-1 levels were increased in PET and HDPE (virgin and aged), in LDPE (virgin), and in PP (aged). The inflammatory panel highlighted an increase in IL-6 in PET (virgin and aged) and, for TNF-alpha, in PET, PP, and LDPE (virgin and aged).

Exposure to PS, HDPE, and LDPE induced pronounced, time-dependent alterations in oxylipin profiles relative to controls, whereas PET and PP elicited no significant temporal changes. Levels of 5-F2t-isoprostane, PGE2, TXB2, and 12-HETE increased up to day 4, followed by a decline at day 7. In contrast, the pro-resolving mediator lipoxin-B4 (LXB4) was elevated on days 4 and 7 compared with day 2. Arachidonic acid levels increased at day 4 and remained stable at day 7, indicating that the late reduction in pro-inflammatory oxylipins was not due to substrate depletion. In any case, aged microplastics consistently induced stronger effects than virgin materials.

Given their large particle size (hundreds of µm), which precludes cellular internalization, these findings suggest that surface-mediated interactions between MPs and the cardiomyocyte membrane drive oxidative stress, inflammation, AA mobilization, and subsequent lipid mediator reprogramming. Overall, the data support a polymer- and aging-dependent, biphasic response characterized by early oxidative and inflammatory activation followed by engagement of endogenous pro-resolving pathways. These results highlight the critical role of microplastic physicochemical properties in modulating cardiac lipid signalling and stress responses.

References

[1] D.H. Lee Circulation, 2024, 150, 908-910.

[2] T. Lomonaco Journal of Hazardous Materials, 2020, 394, 122596.

[3] V. Castelvetro Environmental Science and Pollution Research, 2021, 28, 46764-46780.

[4] D. Biagini Scientific Reports, 2025, 15, 12483.

Prof. Tommaso Lomonaco