Abstract 533: Micro RNA-based Strategy to Preserve Endothelial Function After Angioplasty
Coronary artery disease is currently a leading cause of death worldwide. Despite all the benefits of drug-eluting stents (DES), concerns have been raised over their long-term safety, with particular reference to stent thrombosis due to delayed endothelial cell (EC) coverage. Here we describe a method that exploits the endogenous miRNAs to specifically inhibit vascular smooth muscle cell (VSMC) proliferation, the major cause of restenosis, without affecting re-endothelialization. By inserting four target sequences of the EC specific mir-126 into the 3’UTR of p27 expressing adenoviruses (p27-126TS), we were able to specifically inhibit VSMC proliferation and migration while EC were able to proliferate, migrate and form capillary-like networks. Balloon injured rat carotid artery infected with p27-126TS viruses exhibited complete inhibition of restenosis with complete re-endothelialization after two weeks (Fig. A). Moreover, hypercoagulability assessed by measuring plasma levels of D-dimer in the serum of rats treated with the p27-126TS was similar to the non-injured control (Fig. B). Finally, the vasodilatative response to acetylcholine of balloon injured carotid arteries treated with p27-126TS adenovirus were comparable to those of the control-noninjured vessel (Fig. C). This discovery may ultimately lead to a safer therapy than the non-selective DES and may diminish the need for prolonged dual antiplatelet therapy following percutaneous coronary intervention.
- © 2013 by American Heart Association, Inc.