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. (IJCEM1007005).
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. E-mail: firstname.lastname@example.org