Cold exposure protects against medial arterial calcification development via autophagy

Abstract

Medial arterial calcification (MAC), a systemic vascular disease different from atherosclerosis, is associated with an increased incidence of cardiovascular events. Several studies have demonstrated that ambient temperature is one of the most important factors affecting cardiovascular events. However, there has been limited research on the effect of different ambient temperatures on MAC. In the present study, we showed that cold temperature exposure (CT) in mice slowed down the formation of vitamin D (VD)-induced vascular calcification compared with room temperature exposure (RT). To investigate the mechanism involved, we isolated plasma-derived exosomes from mice subjected to CT or RT for 30 days (CT-Exo or RT-Exo, respectively). Compared with RT-Exo, CT-Exo remarkably alleviated the calcification/senescence formation of vascular smooth muscle cells (VSMCs) and promoted autophagy by activating the phosphorylation of AMP-activated protein kinase (p-AMPK) and inhibiting phosphorylation of mammalian target of rapamycin (p-mTOR). At the same time, CT-Exo promoted autophagy in β-glycerophosphate (β-GP)-induced VSMCs. The number of autophagosomes and the expression of autophagy-related proteins ATG5 and LC3B increased, while the expression of p62 decreased. Based on a microRNA chip microarray assay and real-time polymerase chain reaction, miR-320a-3p was highly enriched in CT-Exo as well as thoracic aortic vessels in CT mice. miR-320a-3p downregulation in CT-Exo using AntagomiR-320a-3p inhibited autophagy and blunted its anti-calcification protective effect on VSMCs. Moreover, we identified that programmed cell death 4 (PDCD4) is a target of miR-320a-3p, and silencing PDCD4 increased autophagy and decreased calcification in VSMCs. Treatment with CT-Exo alleviated the formation of MAC in VD-treated mice, while these effects were partially reversed by GW4869. Furthermore, the anti-arterial calcification protective effects of CT-Exo were largely abolished by AntagomiR-320a-3p in VD-induced mice. In summary, we have highlighted that prolonged cold may be a good way to reduce the incidence of MAC. Specifically, miR-320a-3p from CT-Exo could protect against the initiation and progression of MAC via the AMPK/mTOR autophagy pathway. Graphic Abstract

Alterations of plasma neuron-derived exosomal microRNAs in patients with bipolar disorder

“…Another signi cant nding from our study is the observed increase in levels of hsa-miR-320a-3p, which plays a pivotal role in regulating the AMPK/mTOR autophagy pathway [32]. Vanderplow et al's work sheds light on how any downturn in Akt-mTOR signaling can dent the synaptic structural and functional plasticity in the prefrontal cortex (PFC), ultimately affecting PFC-mediated cognition in patients with BD [33].…”

Diagnostic and prognostic significance of miR-320a-3p in patients with chronic heart failure

“…Wang et al reported that miR-320a accelerated the proliferation of myocardial fibroblasts by regulating the mTOR signaling pathway in HEH2 cells [ 27 ]. Li et al claimed that miR-320a-3p prevented the development of medial arterial calcification through the AMPK/mTOR autophagy pathway [ 28 ]. After searching the published literature, we did find that miR-320a-3p is associated with predicted target genes and associated signaling pathways in animal or cellular models.…”