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Vessel formation and vessel wall biology in disease and medicine

Research project P6/30 (Research action P6)

Persons :

Description :

 This project will explore in an integrated manner the genetic, molecular, and cellular mechanisms underlying i) vessel formation in disease situations, ii) vessel wall pathology, endothelial, endocrine and cardiovascular dysfunction related to metabolic syndrome, and iii) the interactions between vessel formation and metabolic syndrome and its consequences, and their potential mutually modulating effects.

During the previous IAP phase, the majority of the partners of the present proposed network already joined the network P5/02, entitled “Angiogenesis and vessel wall diseases”, in investigations aimed at better understanding the mechanisms of vessel formation and vessel wall biology with a strong focus on adult disease-related processes. The network was evaluated as excellent by the recent ex post evaluation committee, who strongly recommended continuation of the research in a further optimized, cooperative and additionally enforced manner. The design of the present proposal and construction of the consortium indeed complies entirely with these recommendations, and will continue and extend the activities of the P5/02 network in research which remains exclusively disease-oriented and includes both basic research and translational research on the efficacy and safety of specific novel therapy approaches.

The proposed project is organized in 4 workpackages (WPs): a WP with a strong focus on pathological vessel formation (lymph/angiogenesis in disease; WP1); a WP focusing on obesity and endocrine dysfunction -components of metabolic syndrome- and their modulation of angiogenic processes and vice versa (WP2); a WP focusing on the interaction between obesity and other metabolic syndrome components (WP3); and WP4, specifically focusing on the oxidative stress component of metabolic syndrome and cardiovascular dysfunction, including pathologies involving angiogenic growth factors and regulators.

The proposed research is largely based on results and findings from previous work of the partners of the P5/02 network. Partners of the previous network and additional new teams (see below) now constitute an extended network of 8 partners, including one European partner, combining all the specific required expertise in order to efficiently and productively address the different aspects of the proposal. As indicated above, the network is now further strengthened with 3 newly joining young research groups (H. Heimberg, VUB; J. Van de Voorde and J. Haigh, RUG; and I. Struman who joins in with the current partner J.M. Foidart, ULg). These new partners bring in additional, complementary and unique expertise highly relevant to as well as needed within the new research programme. More specifically, VUB will provide additional expertise on endocrine function, which is directly relevant to the research related to metabolic syndrome. RUG has unique expertise in in vivo, in situ and in vitro vascular responsiveness assessment and has generated novel genetic mouse models for angiogenesis research and sophisticated methodology for inducible, tissue-specific transgenesis in the mouse. The expanded ULg team provides access to additional tumour models and to novel gene silencing technology.

Combined application of long-term expertise and state-of-art methodologies, techniques and models available among the partners, will ensure efficient progression along the research lines and successfully achieve the objectives. Methodologies will include the use of relevant preclinical animal models (mouse, rabbit, miniature pig) and appropriate transgenesis and gene transfer approaches; state-of-the-art animal experimentation (models of cardiovascular disease, metabolic syndrome, cancer, ocular disease, etc) and phenotype (various functional assays, PET imaging, telemetry, vasomotor function, etc.); complementary in vitro and ex vivo models; gene or protein profiling and genetic screening to identify or confirm gene/protein involvements, as further detailed in the description of the work.

Extensive exchange of these expertises and knowledge, methodologies, models, tools and materials, and new results and insights, will form the basis for a productive scientific interaction between the partners, will consolidate existing collaborations and open up avenues for additional interaction, and create a scientific environment beneficial to all participating partners including young research teams as well as the pre- and postdoctoral fellows in training at the partner laboratories.

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