MYBPH inhibits vascular smooth muscle cell migration and attenuates neointimal hyperplasia in a rat carotid balloon-injury model

Exp Cell Res. 2017 Oct 1;359(1):154-162. doi: 10.1016/j.yexcr.2017.07.036. Epub 2017 Aug 8.

Abstract

Vascular smooth muscle cell (VSMC) migration is implicated in restenosis. Myosin binding protein H (MYBPH) is capable of reducing cell motility and metastasis. In this study, we sought to determine whether MYBPH is involved in VSMC migration and neointima formation in response to vascular injury. To determine the expression of MYBPH in injured artery, we used a standard rat carotid artery balloon-injury model. In vivo studies have demonstrated that MYBPH is upregulated after vascular injury. VSMCs treated with platelet-derived growth factor (PDGF)-BB displayed increased MYBPH mRNA and protein levels. PDGF-induced VSMC migration was inhibited by adenovirus-mediated expression of MYBPH whereas it was enhanced by small interfering RNA knockdown of MYBPH. The activation of ROCK1 was repressed by MYBPH. Luminal delivery of MYBPH adenovirus to carotid arteries decreased neointimal hyperplasia in vivo. MYBPH may, therefore, serve as a novel therapeutic target for postangioplasty restenosis.

Keywords: MYBPH; Migration; Neointima formation; ROCK1; Vascular smooth muscle cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carotid Artery Injuries / metabolism*
  • Carotid Artery Injuries / pathology*
  • Cell Movement*
  • Cytoskeletal Proteins / metabolism*
  • Disease Models, Animal
  • Enzyme Activation
  • Gene Knockdown Techniques
  • Hyperplasia
  • Muscle, Smooth, Vascular / pathology*
  • Myocytes, Smooth Muscle / metabolism*
  • Neointima / pathology*
  • Rats, Sprague-Dawley
  • rho-Associated Kinases / metabolism

Substances

  • Cytoskeletal Proteins
  • Mybph protein, rat
  • rho-Associated Kinases