Prevention of neointimal formation using miRNA-126-containing nanoparticle-conjugated stents in a rabbit modelReportar como inadecuado




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Background

Despite recent progress with drug-eluting stents, restenosis and thrombosis after endovascular intervention are still major limitations in the treatment of cardiovascular diseases. These problems are possibly caused by inappropriate inhibition of neointimal formation and retardation of re-endothelialization on the surface of the stents. miR-126 has been shown to have the potential to enhance vascular endothelial cell proliferation.

Methods and results

We designed and constructed a 27-nt double strand RNA dsRNA conjugated to cholesterol, which has high membrane permeability, and formed mature miR-126 after transfection. For site-specific induction of miR-126, we utilized poly DL-lactide-co-glycolide nanoparticles NPs. miR-126-dsRNA-containing NPs miR-126 NPs significantly reduced the protein expression of a previously identified miR-126 target, SPRED1, in human umbilical vascular endothelial cells HUVECs, and miR-126 NPs enhanced the proliferation and migration of HUVECs. On the other hand, miR-126 NPs reduced the proliferation and migration of vascular smooth muscle cells, via the suppression of IRS-1. Finally, we developed a stent system that eluted miR-126. This delivery system exhibited significant inhibition of neointimal formation in a rabbit model of restenosis.

Conclusions

miR-126 NP-conjugated stents significantly inhibited the development of neointimal hyperplasia in rabbits. The present study may indicate the possibility of a novel therapeutic option to prevent restenosis after angioplasty.



Autor: Masayasu Izuhara, Yasuhide Kuwabara, Naritatsu Saito, Erika Yamamoto, Daihiko Hakuno, Yasuhiro Nakashima, Takahiro Horie, Osamu B

Fuente: http://plos.srce.hr/



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