Local Anti-miR Delivery

miRNA-specific regulation of gene expression has now been implicated in the development of several pathophysiologic processes that underlie diseases of the cardiovascular system.1 As such, miRNAs have become attractive targets for the design of potential therapies aimed at atherosclerosis, myocardial infarction, and cardiomyopathy. However, their ability to control multiple pathways in different tissue types leads to the possibility that their inhibition will result in unwanted effects. One challenge has therefore been the development of tissue- or cell-specific miRNA therapeutic approaches that avoid these off-target effects. In this issue of Atherosclerosis, Thrombosis, and Vascular Biology , Wang et al report the targeted delivery of miR-21 inhibitors for the treatment of arterial in-stent restenosis (ISR) and demonstrate how using an anti-miR-21–coated stent approach overcomes untoward side effects of systemic anti-miR-21 delivery (Figure).2Figure. Anti-miR-21–coated stents prevent myointimal hyperplasia. In a stented artery ( top ), stent deployment compresses an existing plaque to open up the arterial lumen. Twenty-eight days later, significant myointimal hyperplasia occurs with a bare metal stent ( left ), resulting in restenosis and renarrowing of the vessel lumen. With an anti-miR-21–coated stent ( right ), there is reduced smooth muscle cell (SMC) proliferation, increased expression of miR-21 target genes, and reduced myointimal hyperplasia resulting in a preservation of lumen …