Suppression of cyclin D1 by plasmid-based short hairpin RNA ameliorated experimental pulmonary vascular remodeling

Microvasc Res. 2013 Nov:90:144-9. doi: 10.1016/j.mvr.2013.07.012. Epub 2013 Aug 13.

Abstract

Our previous study has demonstrated that a plasmid-based short hairpin RNA (shRNA) against cyclin D1 could attenuate the pulmonary artery smooth muscle cell (PASMC) proliferation and pulmonary vascular remodeling in smoking rats. In this report, we examined the efficiency of this shRNA plasmid in monocrotaline-induced pulmonary vascular remodeling. A single injection of monocrotaline induced pulmonary vascular remodeling and cyclin D1 over-expression in pulmonary vascular smooth muscle. The shRNA successfully suppressed the up-regulation of cyclin D1 in pulmonary vessels of monocrotaline-treated rats. Moreover, this shRNA decreased the percentage of muscularized vessels and the wall thickness of pulmonary vessels. So, we concluded that plasmid-based shRNA against cyclin D1 ameliorated pulmonary vascular remodeling in monocrotaline-treated rats. Cyclin D1 might be a potential target for the therapy of pulmonary vascular remodeling and pulmonary hypertension.

MeSH terms

  • Animals
  • Cell Proliferation
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Disease Models, Animal
  • Down-Regulation
  • Genetic Therapy / methods*
  • Genetic Vectors*
  • Hypertension, Pulmonary / chemically induced
  • Hypertension, Pulmonary / genetics
  • Hypertension, Pulmonary / metabolism
  • Hypertension, Pulmonary / pathology
  • Hypertension, Pulmonary / therapy*
  • Male
  • Monocrotaline
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology
  • Pulmonary Artery / metabolism
  • Pulmonary Artery / pathology
  • RNA Interference*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Transfection*

Substances

  • Ccnd1 protein, rat
  • RNA, Small Interfering
  • Cyclin D1
  • Monocrotaline