Objetivos e Atividades
Our objectives are to:
1. thoroughly escribe and quantify the response to stretch in: (i) different experimental set-ups ranging from the in vitro (skinned cardiomyocytes), ex vivo tissue and organ level,to the in vivo intact organism, (ii) healthy and diseased animals from different species including a large animal model,and also (iii) cardiac surgical patients;
2. dissect the subcellular pathways underlying the diastolic response to stretch, focusing on the activities of PKG and CaMK II;
3. demonstrate that impaired PKG signalling is responsible for inefficient responses to stretch;
4. further establish the role of titin in the response;
5. evaluate the potential of myocardial stretch as a diagnostic tool in HFpEF in small and large animal models by performing haemodynamic stress experiments;
6. extend our findings from animal models to the patient (cardiac surgical patients);
7. evaluate the therapeutic potential of enhancing the PKG pathway in a preclinical trial;
Resultados Esperados/Atingidos
Avaliações em curso |