title: The MicroRNAs in the Pathogenesis of Metabolic Memory.
abstract: "Metabolic memory" is identified as a phenomenon that previous exposure to hyperglycemia results in the long-lasting deleterious effects on cardiovascular events. More and more researches show that epigenetics plays an important role in the pathogenesis of metabolic memory. It remains unclear whether microRNA (miRNA) dysfunctions participate in the event. In this study, the miRNA arrays on human aortic endothelial cells were adopted to seek the miRNAs that may be involved in the metabolic memory and were verified in vivo and in vitro. Sixteen miRNAs were found differentially expressed. Among these miRNAs, the expressions of miR-125b, miR-146a-5p, and miR-29a-3p were associated with persistent impaired endothelial function and altered proinflammatory gene expressions, including nuclear factor-κB (NF-κB) subunit p65. Direct inhibition of miR-125b expression or increased miR-146a-5p expression blunted NF-κB signals and improved the endothelial function. Luciferase reporter assays confirmed the biochemical relationship for miR-125b targeting on TNF-α-induced protein 3 and miR-146a-5p targeting on TNF receptor-associated factor 6 and IL-1 receptor-associated kinase 1 during the activation of NF-κB pathway. Thus, our findings demonstrate that glucose induced changes in miR-125b and miR-146a-5p are related to the long-lasting activation of NF-κB pathway and contribute to follow-up metabolic memory.
authors.affiliation: Departments of Endocrinology (X.Z., Y.L., L.C., G.L., T.Z.) and Orthopedics (Y.F.), Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; and Department of Endocrinology (J.Z.), Yichang Central People's Hospital, First Clinical Medical College of Three Gorges University, Yichang 443003, China.
authors.forename: Xueyu
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Departments of Endocrinology (X.Z., Y.L., L.C., G.L., T.Z.) and Orthopedics (Y.F.), Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; and Department of Endocrinology (J.Z.), Yichang Central People's Hospital, First Clinical Medical College of Three Gorges University, Yichang 443003, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Departments of Endocrinology (X.Z., Y.L., L.C., G.L., T.Z.) and Orthopedics (Y.F.), Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; and Department of Endocrinology (J.Z.), Yichang Central People's Hospital, First Clinical Medical College of Three Gorges University, Yichang 443003, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Departments of Endocrinology (X.Z., Y.L., L.C., G.L., T.Z.) and Orthopedics (Y.F.), Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; and Department of Endocrinology (J.Z.), Yichang Central People's Hospital, First Clinical Medical College of Three Gorges University, Yichang 443003, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Liu
authors.affiliation: Departments of Endocrinology (X.Z., Y.L., L.C., G.L., T.Z.) and Orthopedics (Y.F.), Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; and Department of Endocrinology (J.Z.), Yichang Central People's Hospital, First Clinical Medical College of Three Gorges University, Yichang 443003, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Departments of Endocrinology (X.Z., Y.L., L.C., G.L., T.Z.) and Orthopedics (Y.F.), Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; and Department of Endocrinology (J.Z.), Yichang Central People's Hospital, First Clinical Medical College of Three Gorges University, Yichang 443003, China.
authors.forename: Tianshu
authors.initials: T
authors.lastname: Zeng
authors.affiliation: Departments of Endocrinology (X.Z., Y.L., L.C., G.L., T.Z.) and Orthopedics (Y.F.), Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; and Department of Endocrinology (J.Z.), Yichang Central People's Hospital, First Clinical Medical College of Three Gorges University, Yichang 443003, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001011:Aorta / Q000503:physiopathology; D002478:Cells, Cultured; D003925:Diabetic Angiopathies / Q000209:etiology*; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D016328:NF-kappa B; C000602677:TNFAIP3 protein, rat; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3