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Potential Mechanisms of Aortic Medial Degeneration Promoted by Co-Exposure to Microplastics and Lead

Xiaoping Xie,Kexin Wang,Xiaoyan Shen,Xu li,Su Wang,Shun Yuan,Bowen Li,Zhiwei Wang

Microplastics (MPs) have attracted widespread attention because they can lead to combined toxicity by adsorbing heavy metals from the environment. Exposure to lead (Pb), a frequently adsorbed heavy metal by MPs, is common. In the current study, the coexistence of MPs and Pb was assessed in human samples. Then, mice were used as models to examine how co-exposure to MPs and Pb promotes aortic medial degeneration. The results showed that MPs and Pb co-exposure were detected in patients with aortic disease. In mice, MPs and Pb co-exposure promoted the damage of elastic fibers, loss of vascular smooth muscle cells (VSMCs), and release of inflammatory factors. In vitro cell models revealed that co-exposure to MPs and Pb induced excessive reactive oxygen species generation, impaired mitochondrial function, and triggered PANoptosome assembly in VSMCs. These events led to PANoptosis and inflammation through the cAMP/PKA-ROS signaling pathway. However, the use of the PKA activator 8-Br-cAMP or mitochondrial ROS scavenger Mito-TEMPO improved, mitochondrial function in VSMCs, reduced cell death, and inhibited inflammatory factor release. Taken together, the present study provided novel insights into the combined toxicity of MPs and Pb co-exposure on the aorta. Environmental Implication Microplastics (MPs) and Lead (Pb) are pervasive in the environment, yet studies on the cardiovascular toxicity of MPs and Pb co-exposure remain scarce. This research investigates the effects of MPs and Pb co-exposure on aortic medial degeneration (AMD). The findings reveal the presence of MPs and Pb exposure in patients. Co-exposure to MPs and Pb accelerates AMD in the mice. Further experiments confirm that co-exposure to MPs and Pb affects vascular smooth muscle cell activity and inflammation by regulating the cAMP/PKA pathway and mitochondrial function. Our study offers new insights into the synergistic toxic mechanisms of MPs and Pb.