Abstract
BackgroundType 2 diabetes mellitus (T2DM) is an independent risk factor of cardiovascular disease (CVD), however, the underlying mechanisms are largely unknown. Using non-atherosclerotic internal thoracic arteries (ITAs) obtained from coronary artery bypass grafting, we previously identified a distinct elevation in the level of proteins comprising the arterial basement membrane in T2DM patients not treated with metformin. Altered transcription of genes encoding these proteins has not been observed, indicating alternative mechanisms of dysregulation.MethodsIn this study we screened for differential expression of arterial microRNAs (miRNAs) in T2DM patients to test the hypothesis that the arterial protein signature of diabetic patients is associated with dysregulation at the miRNA level, and further to lay the foundation for novel hypotheses addressing the increased CVD risk of T2DM patients. MiRNA isolated from fresh frozen ITAs [from 18 T2DM- (10 of which were subject to metformin treatment) and 30 non-diabetes mellitus (non-DM) patients] were analyzed by microarray, and miRNAs isolated from formalin-fixated paraffin-embedded (FFPE) ITAs were analyzed by quantitative PCR (qPCR) in an independent study group [26 T2DM- (15 of which were subject to metformin treatment) and 26 non-DM patients] to determine expression levels of miRNAs in a pre-defined panel of 12 miRNAs.ResultsUnexpectedly, no miRNAs were found to be affected by T2DM status in either of the two study groups.ConclusionsOur data suggest that alternatives to microRNA dysregulation underlie T2DM-associated protein changes in non-atherosclerotic arteries.
Highlights
Type 2 diabetes mellitus (T2DM) is an independent risk factor of cardiovascular disease (CVD), the underlying mechanisms are largely unknown
Tissue and study subjects One hundred internal thoracic artery (ITA) systematically collected in the Odense Artery Biobank over a 9-year period from coronary artery by-pass grafting (CABG) were analyzed in this study
T2DM and non-diabetes mellitus (non-DM) patients in study group 1 differed on glycated hemoglobin (HbA1c) and body mass index (BMI), while in study group 2, these groups differed on HbA1c, high-density lipoprotein (HDL) and triglycerides (TAG) (Table 1)
Summary
Type 2 diabetes mellitus (T2DM) is an independent risk factor of cardiovascular disease (CVD), the underlying mechanisms are largely unknown. Diabetic patients treated with metformin, a standard drug with beneficial effects on glucose metabolism and diabetes-related complications [9], had significantly reduced levels of these proteins as compared to non-metformin treated diabetic patients [8]. These protein alterations do not appear to be accompanied by changes of the corresponding gene transcripts [10, 11]. The idea of microRNA (miRNA)-mediated epigenetic regulation is appealing since COL4A1 and COL4A2 mRNA (encoding the α1- and α2-chain of collagen IV, respectively) are subject to pronounced regulation by miRNAs miR-29a and miR-29b [12,13,14,15,16,17], which are expressed in vascular tissue [18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
