PMID- 37021573 OWN - NLM STAT- MEDLINE DCOM- 20230526 LR - 20230825 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 43 IP - 6 DP - 2023 Jun TI - Sleep Deprivation Promotes Endothelial Inflammation and Atherogenesis by Reducing Exosomal miR-182-5p. PG - 995-1014 LID - 10.1161/ATVBAHA.123.319026 [doi] AB - BACKGROUND: Insufficient or disrupted sleep increases the risk of cardiovascular disease, including atherosclerosis. However, we know little about the molecular mechanisms by which sleep modulates atherogenesis. This study aimed to explore the potential role of circulating exosomes in endothelial inflammation and atherogenesis under sleep deprivation status and the molecular mechanisms involved. METHODS: Circulating exosomes were isolated from the plasma of volunteers with or without sleep deprivation and mice subjected to 12-week sleep deprivation or control littermates. miRNA array was performed to determine changes in miRNA expression in circulating exosomes. RESULTS: Although the total circulating exosome levels did not change significantly, the isolated plasma exosomes from sleep-deprived mice or human were a potent inducer of endothelial inflammation and atherogenesis. Through profiling and functional analysis of the global microRNA in the exosomes, we found miR-182-5p is a key exosomal cargo that mediates the proinflammatory effects of exosomes by upregulation of MYD88 (myeloid differentiation factor 88) and activation of NF-kB (nuclear factor kappa-B)/NLRP3 pathway in endothelial cells. Moreover, sleep deprivation or the reduction of melatonin directly decreased the synthesis of miR-182-5p and led to the accumulation of reactive oxygen species in small intestinal epithelium. CONCLUSIONS: The findings illustrate an important role for circulating exosomes in distant communications, suggesting a new mechanism underlying the link between sleep disorder and cardiovascular disease. FAU - Li, Xiao AU - Li X AD - School of Basic Medical Sciences, and The Second Affiliated Hospital of Shandong First Medical University & Shandong Academy of Medical Science, Jinan, China (X.L., Y.C., X.X., C.W., X.L., C.Y., Z.Z., G.S.). FAU - Cao, Ying AU - Cao Y AD - School of Basic Medical Sciences, and The Second Affiliated Hospital of Shandong First Medical University & Shandong Academy of Medical Science, Jinan, China (X.L., Y.C., X.X., C.W., X.L., C.Y., Z.Z., G.S.). FAU - Xu, Xinxin AU - Xu X AD - School of Basic Medical Sciences, and The Second Affiliated Hospital of Shandong First Medical University & Shandong Academy of Medical Science, Jinan, China (X.L., Y.C., X.X., C.W., X.L., C.Y., Z.Z., G.S.). FAU - Wang, Chongyue AU - Wang C AD - School of Basic Medical Sciences, and The Second Affiliated Hospital of Shandong First Medical University & Shandong Academy of Medical Science, Jinan, China (X.L., Y.C., X.X., C.W., X.L., C.Y., Z.Z., G.S.). FAU - Ni, Qingbin AU - Ni Q AD - Hydrogen medicine center, Tai 'an City Central Hospital, China (Q.N.). FAU - Lv, Xiang AU - Lv X AD - School of Basic Medical Sciences, and The Second Affiliated Hospital of Shandong First Medical University & Shandong Academy of Medical Science, Jinan, China (X.L., Y.C., X.X., C.W., X.L., C.Y., Z.Z., G.S.). FAU - Yang, Chao AU - Yang C AD - School of Basic Medical Sciences, and The Second Affiliated Hospital of Shandong First Medical University & Shandong Academy of Medical Science, Jinan, China (X.L., Y.C., X.X., C.W., X.L., C.Y., Z.Z., G.S.). FAU - Zhang, Zhaoqiang AU - Zhang Z AD - School of Basic Medical Sciences, and The Second Affiliated Hospital of Shandong First Medical University & Shandong Academy of Medical Science, Jinan, China (X.L., Y.C., X.X., C.W., X.L., C.Y., Z.Z., G.S.). FAU - Qi, Xufeng AU - Qi X AUID- ORCID: 0000-0002-5911-071X AD - Key Laboratory of Regenerative Medicine of Ministry of Education, Department of Developmental & Regenerative Biology, Jinan University, Guangzhou, China (X.Q.). FAU - Song, Guohua AU - Song G AUID- ORCID: 0000-0002-3799-8420 AD - School of Basic Medical Sciences, and The Second Affiliated Hospital of Shandong First Medical University & Shandong Academy of Medical Science, Jinan, China (X.L., Y.C., X.X., C.W., X.L., C.Y., Z.Z., G.S.). LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230406 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (MicroRNAs) RN - 0 (Mirn182 microRNA, human) SB - IM MH - Humans MH - Animals MH - Mice MH - Endothelial Cells/metabolism MH - Sleep Deprivation/complications/genetics/metabolism MH - *Cardiovascular Diseases/metabolism MH - *MicroRNAs/metabolism MH - *Exosomes/genetics/metabolism MH - Inflammation/genetics/metabolism MH - *Atherosclerosis/genetics/metabolism OTO - NOTNLM OT - atherogenesis OT - endothelial inflammation OT - exosomes OT - melatonin OT - sleep deprivation COIS- Disclosures None. EDAT- 2023/04/07 06:00 MHDA- 2023/05/26 06:42 CRDT- 2023/04/06 05:03 PHST- 2023/05/26 06:42 [medline] PHST- 2023/04/07 06:00 [pubmed] PHST- 2023/04/06 05:03 [entrez] AID - 10.1161/ATVBAHA.123.319026 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2023 Jun;43(6):995-1014. doi: 10.1161/ATVBAHA.123.319026. Epub 2023 Apr 6.