Source: International Congress 2016 – Pulmonary hypertension and pulmonary embolism: from the bench to the bedside
Disease area: Pulmonary vascular diseases

Abstract

Rationale: Imbalance between cell proliferation and apoptotis may underlie the development of PAH. Proteins involved in the apoptosis pathway may play a role in PAH and their inhibition may represent a potential therapeutic target. Survivin is a member of the apoptosis inhibitor gene family involved in cell proliferation. We aimed to evaluate its potential involvement in the pathogenesis of PAH.Methods: C57/BL6 mice were exposed to hypoxia and SU5416 was subcutaneously injected weekly. Sprague–Dawley rats received a single subcutaneous injection of monocrotaline (MCT); measurements were performed after 4 weeks. Right ventricular systolic pressure (RVSP) was measured by right heart catheterization. Right ventricle (RV) hypertrophy was evaluated by the Fulton index. Vascular remodeling and survivin expression were assessed in lung sections by immunohistochemistry for smooth muscle actin (SMA) and survivin respectively. Survivin gene expression was evaluated by qPCR.Results: Both animal models showed an increase in the RVSP (mice: 22±3 vs 36±10mmHg (p=0.014); and rats: 26±1 vs 71±14mmHg (p<0.001) in controls vs treated respectively). SU5416+hypoxia-treated mice developed vascular remodeling (7.1±3.4 SMA⁺ vessels/mm² in controls and 15.9±4.0 in SU5416+hypoxia (p=0.0002)) and showed a trend for an increased expression of survivin in intrapulmonary arteries. Survivin gene expression was 5 fold higher in SU5416+hpoxia mice (p<0.0001) and 2 fold in MCT rats (p=0.0002) compared to controls.Conclusions: Survivin expression is increased in two different experimental models of PAH, suggesting that it might be involved in the pathogenesis of the disease. Funded by Grants from FIS (PI14/00782), SEPAR, SOCAP and FCHP.


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Isabel Blanco (Barcelona, Spain), Isabel Blanco, Elisabet Ferrer, Susana Maqueda, Tanja Paul, Neus Luque, Olga Tura-Ceide, Victor Ivo Peinado, Joan Albert Barbera. Role of survivin in experimental models of pulmonary arterial hypertension. Eur Respir J 2016; 48: Suppl. 60, 2483

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