Effects of erythropoietin on advanced pulmonary vascular remodelling

M. E. van Albada*, G. J. du Marchie Sarvaas, J. Koster, M. C. Houwertjes, R. M. F. Berger, R. G. Schoemaker

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)

Abstract

Erythropoietin (EPO) mobilises endothelial progenitor cells and promotes neovascularisation in heart failure. The present authors studied the effects of EPO on pulmonary vascular and cardiac remodelling in a model for flow-associated pulmonary arterial hypertension (PAH). PAH was induced in adult male Wistar rats by the injection of monocrotaline combined with an abdominal aortocaval shunt 1 week later (PAH or experimental group). Immediately afterwards, rats were randomised into those who received treatment with EPO (PAH+EPO group) and controls. Pulmonary and systemic haemodynamics, and right ventricular and pulmonary vascular remodelling were evaluated 3 weeks later. Vascular occlusion of the intra-acinar pulmonary vessels (13.4 +/- 0.7 versus 16.7 +/- 1.3% in PAH+EPO and PAH, respectively) and medial wall thickness of the pre-acinar arteries (wall-to-lumen ratio 0.13 +/- 0.01 versus 0.17 +/- 0.01 in PAH+EPO and PAH, respectively) decreased after treatment with EPO. Moreover, right ventricular capillary density was increased by therapy (2,322 +/- 61 versus 2,100 +/- 63 capillaries mm(-2) in PAH+EPO and PAH, respectively). Increased mean pulmonary arterial pressure and decreased right ventricular contractility in the model were not altered by EPO treatment. In this rat model of flow-associated pulmonary arterial hypertension, erythropoietin treatment beneficially affected pulmonary vascular and cardiac remodelling. These histopathological effects were not accompanied by significantly improved haemodynamics.

Original languageEnglish
Pages (from-to)126-134
Number of pages9
JournalEuropean Respiratory Journal
Volume31
Issue number1
DOIs
Publication statusPublished - Jan-2008

Keywords

  • heart failure
  • histopathology
  • pulmonary circulation
  • ventricular function
  • ENDOTHELIAL GROWTH-FACTOR
  • MARROW-DERIVED CELLS
  • PROGENITOR CELLS
  • ARTERIAL-HYPERTENSION
  • EXPERIMENTAL-MODEL
  • REPERFUSION INJURY
  • HEME OXYGENASE-1
  • TYROSINE KINASE
  • GENE-TRANSFER
  • FETAL SHEEP

Cite this