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Phenotyping the Biologic Diversity of Endothelial Cells


Background: The microvasculature of elderly population is frequently affected by disease states such as diabetes and ischemia. Our group has set up new gene transfer approaches for the prevention and cure of diabetic microangiopathy. For translating these pre-clinical successes into clinical deliverables, it is necessary to gain a deeper understanding of downstream pathways and effector proteins. Serial analysis of gene expression (SAGE) and proteomics represent potent instruments to achieve the goal. Alth ough these methodologies are becoming accessible to individual investigators, the range of options can be bewildering for the uninitiated so as to require transfer of knowledge interventions across European laboratories. Aim: The present project is aimed t o characterize the proteomic diversity of diabetic endothelial cells. In particular, the proposal focuses on the identification of RNA transcripts or proteins contributing to the premature senescence of vascular endothelium in diabetic animal models and th en correct these defects by appropriate gene therapy approaches. Significance of Transfer of Knowledge: The host institution has an established experience in angiogenesis-related diseases, which will allow to peak up instantaneous advantage of new instrume nts for proteomic analysis. Absorbing competence in this field will put our laboratory -located in a less favoured region with the highest incidence of diabetes- in the conditions to provide the first description of proteomic diversity of diabetic microvas culature, thereby facilitating the introduction of new mechanistic therapeutic approaches.

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