Adipose extracellular vesicles carrying miR-210-3p drive macrophage inflammation and nicotine-induced atherosclerosis

Visceral adipose tissue (VAT)-derived extracellular vesicles (EVs) have emerged as key mediators of inter-organ communication, yet their role in nicotine-induced atherosclerosis remains poorly defined. Here, we demonstrate that nicotine markedly enhances secretion of VAT-EVs and that these EVs are preferentially internalized by macrophages within atherosclerotic plaques, thereby accelerating lesion progression. Functionally, nicotine-induced VAT-EVs promote macrophage inflammation, oxidative stress, and foam cell formation. High-throughput profiling identified miR-210-3p as a dominant pro-atherogenic cargo within VAT-EVs, and its inhibition significantly attenuated nicotine-induced atherosclerosis <i>in vivo</i>. Mechanistically, miR-210-3p directly targets Krüppel-like factor 7 (KLF7), amplifying macrophage inflammatory responses and promoting plaque progression. Collectively, these findings uncover a previously unrecognized role of adipose-derived EVs in smoking-related vascular injury and highlight EV-derived miR-210-3p as a promising therapeutic target in nicotine-associated atherosclerosis.