Systemic single administration of anti-inflammatory microRNA 146a-5p loaded in polymeric nanomedicines with active targetability attenuates neointimal hyperplasia by controlling inflammation in injured arteries in a rat model

FASEB J. 2022 Sep;36(9):e22486. doi: 10.1096/fj.202101481R.

Abstract

Neointimal hyperplasia (NIH) after revascularization is a key unsolved clinical problem. Various studies have shown that attenuation of the acute inflammatory response on the vascular wall can prevent NIH. MicroRNA146a-5p (miR146a-5p) has been reported to show anti-inflammatory effects by inhibiting the NF-κB pathway, a well-known key player of inflammation of the vascular wall. Here, a nanomedicine, which can reach the vascular injury site, based on polymeric micelles was applied to deliver miR146a-5p in a rat carotid artery balloon injury model. In vitro studies using inflammation-induced vascular smooth muscle cell (VSMC) was performed. Results showed anti-inflammatory response as an inhibitor of the NF-κB pathway and VSMC migration, suppression of reactive oxygen species production, and proinflammatory cytokine gene expression in VSMCs. A single systemic administration of miR146a-5p attenuated NIH and vessel remodeling in a carotid artery balloon injury model in both male and female rats in vivo. MiR146a-5p reduced proinflammatory cytokine gene expression in injured arteries and monocyte/macrophage infiltration into the vascular wall. Therefore, miR146a-5p delivery to the injury site demonstrated therapeutic potential against NIH after revascularization.

Keywords: anti-inflammatory effect; miR146a-5p; microRNA; nanomedicine; neointimal hyperplasia; polyion complex micelle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Arteries
  • Carotid Artery Injuries* / metabolism
  • Cell Proliferation
  • Cytokines / metabolism
  • Female
  • Hyperplasia / metabolism
  • Inflammation / metabolism
  • Male
  • MicroRNAs* / metabolism
  • Muscle, Smooth, Vascular / metabolism
  • NF-kappa B / metabolism
  • Nanomedicine
  • Neointima / drug therapy
  • Neointima / metabolism
  • Neointima / prevention & control
  • Rats

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • MicroRNAs
  • NF-kappa B