title: Effects of erythropoietin on advanced pulmonary vascular remodelling.
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 x 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.
authors: Beatrix Children's Hospital, University Medical Center Groningen, Postbus 30.001, 9700 RB Groningen, The Netherlands. m.e.van.albada@bkk.umcg.nl.
authors: M E
authors: ME
authors: van Albada
authors: G J
authors: GJ
authors: du Marchie Sarvaas
authors: J
authors: J
authors: Koster
authors: M C
authors: MC
authors: Houwertjes
authors: R M F
authors: RM
authors: Berger
authors: R G
authors: RG
authors: Schoemaker
mesh_terms: D000818:Animals; D004921:Erythropoietin / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000473:pathology; D006976:Hypertension, Pulmonary / Q000628:therapy; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D020257:Ventricular Remodeling
chemical_list: D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D016686:Monocrotaline