Diabetic Endothelial Dysfunction
Coordinator: Raquel Seiça
Phone: +351 239480022
Fax: +351 239480217
Email: raquelsc@ci.uc.pt
General Objectives
IBILI has over the past years committed a great effort to bring together clinicians and basic scientists to elucidate critical molecular mechanisms that may contribute to cell injury and tissue damage on diabetes. A better understanding of the mechanisms of disease may further help to develop innovative strategies to delay or prevent diabetic complication. This research line involves an integrated multidisciplinary approach to diabetic disease and brings together areas such as ophthalmology, physiology, cardiology and neurosciences.
Vascular dysfunction is a common thread to a number of diabetic complications including retinopathy, nephropathy and heart disease. Diabetes exerts its greatest impact throughout the vascular system. The effect includes the well described consequence of small vessel diseases leading to serious complications, but also a substantial predisposition to premature and accelerated disorder of large blood vessel, macrovascular disease. Indeed, leakage of blood from damaged small blood vessels in the eye can lead to macular oedema, while retinal ischemia can lead to neovascularization of the retina associated with progression of diabetic retinopathy. Diabetic nephropathy is also caused by angiopathy of the capillaries supplying the kidney, leading to kidney failure, while neuropathic disorders associated with diabetes are thought to be the result of damage to the blood vessels supplying nerves. The effect of diabetes on large vessels can be seen among others in coronary arteries. The heart in diabetes is affected in different ways, with variable contribution from myocardial dysfunction, autonomic neuropathy and ischaemic heart disease. The latter, as a consequence of the coronary occlusive process, contributes to substantial morbidity and mortality that arises from large vessel disease in diabetes.
Main Achievements
The mechanisms that lead to endothelial dysfunction are still unclear but are likely to be multifactorial. We have recently made some progress in identifying new mechanism whereby glycolytic intermediates may account for the loss of tissue response to hypoxia resulting in cell death and tissue damage. For example we have shown that methylglyoxal, which is increased in diabetes, may disrupt cell response to hypoxia, leading to apoptotic cell death. We have further show that mitochondrial dysfunction is critically involved in cell response to insulin both in animal and cell models of diabetes. By understanding the molecular mechanisms an the different players involved in such de-regulation it is possible to design new pharmacological or gene-based therapies to prevent or treat endothelial dysfunction associated with diabetes. Moreover this group has an extensive expertise in animal models of diabetes as well as on the characterization of diabetesassociated phenotypes in retina, kidney, heart and brain. Therefore, any putative therapeutic approach can be easily tested and its efficiency assessed in animal models such as GK mice.
PI and Researchers
Raquel Seiça
Cristina Sena
Lino Goncalves
Luís Providência
Pedro Monteiro
M.Sc. and Ph.D. Students
Joana Crisóstomo
Lisa Rodrigues
Marta Paiva
Paulo Matafome
Pedro Fonseca
Raquel Carreira
Rui Alves
Sergio Lemos
Teresa Louro