Long-chain chlorinated paraffins (LCCPs) exposure causes senescence and inflammatory damage in cardiomyocytes

Humans can be exposed to LCCPs through air and diet, leading to their accumulation in the body. Given the significance of understanding potential health risks, a thorough investigation into the detrimental health impacts of LCCPs is paramount. In this study, we conducted a series of experiments to investigate the effects of LCCPs on cardiomyocytes, employing techniques such as flow cytometry, western-blot, indirect immunofluorescence, and confocal microscopy. We initially observed that LCCPs caused senescence damage to cardiomyocytes. Under the stimulation of LCCPs, the number of SA-β-Gal positive cardiomyocytes increased, along with an elevation in the protein expression levels of cellular senescence markers (p21, p16). The cell cycle was arrested in the S phase. Subsequently, we observed that LCCPs also induced an increase in ROS and inflammatory cytokines (IL-6, IL-8, TNF-α), as well as a decrease in MMP in cardiomyocytes. Mechanistic studies revealed that LCCPs activated the innate immune response pathway-cGAS-STING pathway, and the cellular senescence damage caused by LCCPs was alleviated upon the addition of a cGAS-STING inhibitor. In conclusion, our findings suggest that LCCPs can induce aging damage in cardiomyocytes by activating the cGAS-STING signaling pathway. This study indicates that LCCPs possesses potential cardiotoxicity and offers necessary experimental data for their rational and regulated utilization.