Survivin and Smac/DIABLO: role of apoptosis in experimental PAH

• Autor(a) principal: Justino, Joana Filipa Fernandes Mendes
• Data de Publicação: 2013
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/13362
• topic: Bioquímica clínica; Hipertensão pulmonar; Apoptose

Pulmonary hypertension (PH) is a multifactorial, progressive disease, characterized by vasoconstriction, pulmonary vascular remodelling and thrombosis in situ, which lead to augmentation of pulmonary arterial pressure and pulmonary vascular resistance, culminating in right heart failure and ultimately in dead. Pulmonary vascular remodelling, which is one of the major contributors to the development and progression of PH, is characterized by excessive cellular proliferation and reduced apoptosis. However, little is known about the molecular mechanisms underlying this imbalance. So, the present work aimed to study the contribution of apoptosis to the pathogenesis of PAH, through the analysis of cardiac and pulmonary expression of survivin and Smac/DIABLO along hemodynamic and morphometric alterations in an animal model of monocrotaline (MCT)-induced PAH. Results showed that cardiomyocytes were hypertrophied 7 days after MCT injection, preceeding hemodynamic alterations which were only present at day 21. Seven days after MCT administration, survivin overexpression was notorious in the ventricles and progressively increased throughout the development of MCT-induced PAH. On the other hand, although increased 7 days after MCT injection, lung survivin expression progressively decreased between the two days. The upregulation of Smac/DIABLO observed in lung, right and left ventricles 7 days after MCT administration, progressively decreased with the disease progression. In conclusion, data suggest that a deregulation in the balance between survivin and smac/DIABLO might be related with pulmonary vascular remodelling and cardiomyocytes hypertrophy in response to apoptotic stimuli.