Abstract
ObjectiveThe incidence of diabetic atherosclerosis (DA) is increasing worldwide. The study aim was to identify differentially expressed microRNAs (DE-miRs) potentially associated with the initiation and/or progression of DA, thereby yielding new insights into this disease.MethodsMatched iliac artery tissue samples were isolated from 6 male rats with or without DA. The Affymetrix GeneChip microRNA 4.0 Array was used to detect miRs. Differential expression between atherosclerotic group and non-atherosclerotic group samples was analyzed using the Gene-Cloud of Biotechnology Information platform. Targetscan and miRanda were then used to predict targets of DE-miRs. Functions and pathways were identified for significantly enriched candidate target genes and a DE-miR functional regulatory network was assembled to identify DA-associated core target genes.ResultsA total of nine DE-miRs (rno-miR-206-3p, rno-miR-133a-5p, rno-miR-133b-3p, rno-miR-133a-3p, rno-miR-325-5p, rno-miR-675-3p, rno-miR-411-5p, rno-miR-329-3p, and rno-miR-126a-3p) were identified, all of which were up-regulated and together predicted to target 3349 genes. The target genes were enriched in known functions and pathways related to lipid and glucose metabolism. The functional regulatory network indicated a modulatory pattern of these metabolic functions with DE-miRs. The miR-gene network suggested arpp19 and MDM4 as possible DA-related core target genes.ConclusionThe present study identified DE-miRs and miRNA-gene networks enriched for lipid and glucose metabolic functions and pathways, and arpp19 and MDM4 as potential DA-related core target genes, suggesting DE-miRs and/or arpp19 and MDM4 could act as potential diagnostic markers or therapeutic targets for DA.
Highlights
The increasing global prevalence of type-2 diabetes mellitus (T2DM) is a major threat to human health
MicroRNAs, conserved 19–25 nucleotide non-coding RNAs that post-translationally regulate gene expression have become a focus of translational research [10,11,12,13]. miRNAs are known to be involved in the onset and development of several disorders including diabetes and associated complications and regulate biological pathways implicated in DM induced atherosclerosis (DA) [11, 14]. miRNAs or their regulated target genes could
Diabetic atherosclerotic rat model The data on weights and random blood glucose levels of rats after STZ administration are summarized in Fig. 1A, B
Summary
The increasing global prevalence of type-2 diabetes mellitus (T2DM) is a major threat to human health. T2DM leads to vascular disease affecting most blood vessel types. It is associated with a markedly increased incidence of cardiovascular disease (CVD) [1,2,3] including atherosclerosis (AS) affecting the macrovasculature [4, 5]. MiRNAs are known to be involved in the onset and development of several disorders including diabetes and associated complications and regulate biological pathways implicated in DA [11, 14]. MiRNAs or their regulated target genes could . The present study was designed to yield new insights into miRNAs associated with DA and identify potential molecular targets for novel diagnostics and therapeutic approaches
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