Combined exposure of fine particulate matter and high-fat diet aggravate the cardiac fibrosis in C57BL/6J mice

Abstract

Cardiac fibrosis is associated with fine particulate matter (PM_2.5) exposure. In addition, whether high-fat diet (HFD) could exacerbate the PM_2.5-induced cardiac injury was unevaluated. Thus, this study was aimed to investigate the combined effects of PM_2.5 and HFD on cardiac fibrosis. The echocardiography and histopathological analysis showed that co-exposure of PM_2.5 and HFD had a significant deleterious effect on both cardiac systolic and diastolic function accompanied the myofibril disorder and myocardial fibrosis in C57BL/6 J mice than exposed to PM_2.5 or HFD alone. The augmented oxidative damage and increased α-SMA area percentage were detected in heart tissue of mice exposed to PM_2.5 and HFD together. PM_2.5 upregulated the expressions of cardiac fibrosis-related special markers, including collagen-I, collagen-III, TGF-β1, p-Smad3 and total Smad3, which had more pronounced activations in co-exposure group. Meanwhile, the factorial analysis exhibited the synergistic interaction regarded to the combined exposure of PM_2.5 and HFD. Simultaneously, PM_2.5 and palmitic acid increased intracellular ROS generation and activated the TGF-β1/Smad3 signaling pathway in cardiomyocytes. While the ROS scavenger NAC had effectively attenuated the ROS level and suppressed the TGF-β1/Smad3 signaling pathway. Taken together, our results demonstrated combined exposure to PM_2.5 and HFD could aggravate cardiac fibrosis via activating the ROS/TGF-β1/Smad3 signaling pathway.