IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Clin Exp Med 2010;3(4):332-340

Original Article
Transforming growth factor-β inhibition attenuates pulmonary arterial hypertension
in rats

Aikaterini J. Megalou, Chryssoula Glava, Dimitrios L. Oikonomidis, Agapi Vilaeti, Maria G. Agelaki, Giannis G. Baltogiannis, Apostolos
Papalois, Antonios P. Vlahos, Theofilos M. Kolettis

Department of Cardiology, Medical School, University of Ioannina, Stavrou Niarxou Avenue, 45110, Ioannina, Greece; Department of
Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece; ELPEN Research Laboratory, Pikermi,
Athens, Greece; 4Cardiovascular Research Institute, Ioannina and Athens, Greece; 5Child Health Department, Pediatric Cardiology
Division, University of Ioannina, Ioannina, Greece.

Received July 25, 2010, accepted October 20, 2010, available online October 23, 2010

Abstract: The role of transforming growth factor-β in the pathogenesis of pulmonary arterial hypertension is unclear. We examined the
effects of T9429, an antibody against transforming growth factor-β receptors, on hemodynamic, histologic and functional parameters in
the rat model of monocrotaline-induced pulmonary hypertension. One week after monocrotaline injection (60 mg/kg) in 28 Wistar rats,
T9429 (0.1mg/kg daily) was administered intraperitoneally in 19 rats (268±10g) via a mini-pump for 7 days. One week thereafter, right
ventricular systolic pressure, pulmonary vascular remodeling and exercise tolerance were evaluated. Compared to the monocrotaline
group (25.5±1.9mmHg), right ventricular systolic pressure was lower (p=0.0014) in the monocrotaline+antibody group (18.4±0.
8mmHg). This was translated into attenuated right ventricular hypertrophy (p=0.0063) and longer (p=0.0155) exercise duration (2.08±0.
29min versus 6.19±1.02min). Pulmonary arterial wall thickness (in vessels 50 -200μm) was comparable between the two groups, but
the monocrotaline+antibody group displayed lower number (p<0.0001) of pre-capillary arterioles (<50μm, in 20 randomly selected
fields) with a muscularized media (23.33±3.15 versus 6.64±0.75). Our results suggest that transforming growth factor-β receptor
blockade improves vascular remodeling and attenuates pulmonary hypertension, a finding with potential therapeutic implications.

Keywords: Pulmonary arterial hypertension, transforming growth factor-β, pulmonary vascular remodeling, exercise tolerance

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Address all correspondence to:
Theofilos M. Kolettis, MD, PhD
FESC, Associate Professor in Cardiology
University of Ioannina
1 Stavrou Niarxou Avenue
45110, Ioannina, Greece.
Tel: +30-265-1007227. Fax: +30-265-1007053.