Effects of erythropoietin on advanced pulmonary vascular remodelling.
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.
van Albada
M E
ME
Beatrix Children's Hospital, University Medical Center Groningen, Postbus 30.001, 9700 RB Groningen, The Netherlands. m.e.van.albada@bkk.umcg.nl.
du Marchie Sarvaas
G J
GJ
Koster
J
J
Houwertjes
M C
MC
Berger
R M F
RM
Schoemaker
R G
RG
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
D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D016686:Monocrotaline