 In this study, we found that prolonged cold exposure can reduce the incidence of medial arterial calcification, MAC, through the activation of AMP-activated protein kinase, AMPK, MTOR autophagy pathway. We also discovered that MIR-320a3P from cold-exposed mouse plasma-derived exosomes, CTXO, plays a key role in this process. Further experiments revealed that MIR-320a3P targets programmed cell death 4, PDCD4, and promotes autophagy in vitro and in vivo. Finally, we found that the anti-arterial calcification protective effects of CTXO are largely abolished when PDCD4 is knocked down. Taken together, our findings suggest that prolonged cold exposure may be a good way to reduce the incidence of MAC. This article was authored by Fuxing Zili, GenGLU, Fengshu, and others.