Tesis doctoral de Javier Moral Sanz
Alteraciones vasculares pulmonares e hipertensión pulmonar en modelos experimentales de diabetes background. pulmonary hypertension (ph) is a progressive disease of poor prognosis defined by an increased mean pulmonary artery pressure (mpap) over 25 mmhg. Additionally, the sustained elevation of the pap leads to right ventricle hypertrophy, heart failure and death in approximately 70 of patients within 5 years after diagnosis. Ph is characterized by an increased pulmonary vascular resistance as a consequence of vasoconstriction of pulmonary arteries (pa), pulmonary arteries smooth muscle cell (pasmc) and endothelial cell proliferation leading to pa remodelling and/or thrombosis in situ. Furthermore, ph has a complex physiopathology unlikel y to be explained by a single factor or gene mutation. Thus several factors tightly related to ph in patients and animal models have been described such as mutations or down-regulation of bone morphogenetic protein receptor 2 (bmpr2), pa endothelial dysfunction, lung inflammation, reduced kv current density in pasmc associated to mutations or down-regulation of kv1.5 channels, as well as an imbalance between circulating vasoconstrictor and vasodilator agents. despite the fact that diabetes is st rongly associated with systemic cardiovascular diseases the relationship with pulmonary vascular disease has been almost disregarded. However, recent epidemiological data revealed that diabetes might be a risk factor for pulmonary hypertension. our h ypothesis is that diabetes mellitus could be a predisposing factor for the onset or development of ph, leading to functional, histological and molecular characteristic features of the earliest stages of ph. the general aim of this thesis is to charac terize the lung and pa alterations induced by type 1 diabetes and insulin resistance, focusing on the study of the features of ph and analyze the potential link between diabetes and ph. methods and results. male sprague-dawley rats were injected with saline (control) or streptozotocin (70 mg/kg, type 1 diabetic group). After 6 weeks, pa were mounted for isometric tension recording, and endothelial function was tested by acetylcholine (ach). Protein expression was measured by western blot and sup eroxide production by dihydroethidium staining. Pa from type 1 diabetic rats showed impaired relaxant response to ach and reduced vasoconstrictor response to the nitric oxide synthase (nos) inhibitor l-name, whereas the response to nitroprusside and
Datos académicos de la tesis doctoral «Alteraciones vasculares pulmonares e hipertension pulmonar en modelos experimentales de diabetes«
- Título de la tesis: Alteraciones vasculares pulmonares e hipertension pulmonar en modelos experimentales de diabetes
- Autor: Javier Moral Sanz
- Universidad: Complutense de Madrid
- Fecha de lectura de la tesis: 26/07/2012
Dirección y tribunal
- Director de la tesis
- ángel Cogolludo Torralba
- Tribunal
- Presidente del tribunal: santos Barrigón vázquez
- carmen Valenzuela miranda (vocal)
- alison marion Gurney (vocal)
- José ángel Lorente balanza (vocal)