Role of FoxO1 and apoptosis in pulmonary vascular remolding in a rat model of chronic thromboembolic pulmonary hypertension

Sci Rep. 2017 May 23;7(1):2270. doi: 10.1038/s41598-017-02007-5.

Abstract

To explore the role of FoxO1 and apoptosis in a rat model of chronic thromboembolic pulmonary hypertension (CTEPH). Rats were randomly divided into a sham group (n = 45) and an experimental group (n = 45). Autologous blood clots were injected into rats three times to induce CTEPH. Rats were further divided into three subgroups: a 1-week subgroup (n = 15), a 2-week subgroup (n = 15), and a 4-week subgroup (n = 15). Mean pulmonary arterial pressure (mPAP) and histopathology were evaluated at each time point. FoxO1, Bad, and Bcl-2 levels were examined at each time point using reverse transcription PCR and western blotting. The mPAP and vessel wall area/total area (WA/TA) ratio in the experimental group gradually increased in a time-dependent manner (P < 0.05). Both the mRNA and protein levels of FoxO1 decreased in the CTEPH rats compared to in the sham group. In addition, embolization led to the up-regulation of Bad and the down-regulation of Bcl-2 (P < 0.05). FoxO1 and apoptosis play an important role in the pathogenesis of CTEPH. Apoptosis-resistant pulmonary artery endothelial cells may play an important role in remodeling of the rat pulmonary artery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Blood Pressure
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Gene Expression
  • Hypertension, Pulmonary / etiology*
  • Hypertension, Pulmonary / pathology*
  • Hypertension, Pulmonary / physiopathology
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Pulmonary Artery / metabolism
  • Pulmonary Artery / pathology
  • Pulmonary Embolism / complications*
  • Pulmonary Embolism / pathology
  • RNA, Messenger / genetics
  • Rats
  • Vascular Remodeling* / genetics
  • bcl-Associated Death Protein / genetics
  • bcl-Associated Death Protein / metabolism

Substances

  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-Associated Death Protein
  • Foxo1 protein, rat