Abstract 18304: Identification of MicroRNAs Dysregulated in a Porcine Model of Coronary In-stent Restenosis
Introduction Vascular injury following stent delivery results in proliferation and migration of smooth muscle cells (SMC) leading to in-stent restenosis. MicroRNAs (miRs) are short, non-coding ribonucleic acids that act to control gene expression at a posttranscriptional level. MiR-21 and -221 positively regulate SMC proliferation through modulation of cell-cycle regulators. MiR-143 and -145 are important in the maintenance of vascular SMC in the differentiated state.
Hypothesis We hypothesised that expression patterns of these key regulatory miRs in the vasculature would alter in response to stent-induced injury.
Methods Pigs received standardized bare-metal (cobalt alloy) or drug-eluting (zotarolimus) stents (n=4/group), over-expanded to induce vessel injury, and were euthanized at 0, 7 or 28 days (BMS) and 28 days (DES). Total RNA was extracted from stented tissue. MiR expression levels were determined by quantitative real-time polymerase chain reaction and normalized to miR-199a-3p, a suitable endogenous control with mean cycle threshold + SD 25.70 + 0.84 across all samples. All comparisons made against control vessels (unstented arteries).
Results MiR-21 levels were upregulated at 7 and 28 days in both stent types. No differences were seen between BMS and DES at 28 days. MiR-221 levels were elevated at Day 7 in the BMS group, returning to baseline at 28 days. MiR-145 levels showed immediate downregulation (Day 0) and stayed significantly low in all groups. MiR-143 levels did not show this immediate change, but were otherwise similar to miR-145. Levels of miR-145 only were significantly lower in arteries receiving DES compared with BMS at 28 days (75% vs. 48% downregulation).
Conclusions In conclusion, vascular miRs show altered expression following stent insertion. MiR-145 levels were lower in arteries with DES, in comparison to BMS, at 28 days. This provides potentially important information for future manipulation of miRs in the vessel wall.
- © 2012 by American Heart Association, Inc.