Healing the injured vessel wall using microRNA-facilitated gene delivery

Feinberg, Mark W.

Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Address correspondence to: Mark W. Feinberg, Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, NRB-742F, Boston, Massachusetts 02115, USA. Phone: 617.525.4381; E-mail: [email protected].

Conflict of interest: The author has declared that no conflict of interest exists.

Reference information:J Clin Invest. 2014;124(9):3694-3697. doi:10.1172/JCI77509.

See the related article beginning on page 4102.

Journal of Clinical Investigation 124(9):p 3694-3697, September 2, 2014. | DOI: 10.1172/JCI77509

Drug-eluting stents have emerged as potent weapons in the treatment of patients with symptomatic coronary artery disease by reducing restenosis rates; however, a significant clinical consequence of these stents is delayed reendothelialization, which may increase the risk of late stent thrombosis. In this issue of theJCI, Santulli and colleagues generated an adenovirus that expresses the cyclin-dependent kinase inhibitor p27^Kip1 (p27) and bears four tandem copies of target sequences for the endothelial cell-enriched microRNA (miRNA) miR-126-3p (Ad-p27-126TS) in an attempt to specifically reduce proliferation of vascular smooth muscle cells, but not endothelial cells. Indeed, delivery of Ad-p27-126TS to balloon-injured arteries in rats not only induced faster and more complete reendothelialization, but also effectively improved neointimal hyperplasia, hypercoagulability, and vasoreactivity. Collectively, these findings provide a cogent foundation for the potential therapeutic use of miRNA-facilitated gene delivery strategies to heal vessel wall injury.