Normal tissue function relies on an adequate supply of oxygen through blood vessels. Different pathologies are associated to an excess or a defect of vascularization. Understanding how vessel form would offer therapeutical options to improve and even cure human disorders such as at least preeclampsia, cancers and age related macular degeneration (AMD).

Blood vessels form through different processes such as:
(1) vasculogenesis, the in situ differentiation of precursor cells derived from bone marrow (angioblasts) and
(2) angiogenesis, growth of endothelial sprouts from preexisting vessels.

In addition to blood vessels, lymphatic vessels allow the passage of fluids and delivers molecules within the body. Through their capacity to absorb fluid and to transport white blood cells and antigen-presenting cells, lymphatic vessels are involved in immunity and inflammation. Lymphangiogenesis is also implicated in metastatic spread of tumor cells by providing a route of dissemination. Until recently, despite its implication in numerous pathologies, the lymphatic system has been overshadowed by the greater emphasis placed on the blood vascular system.

Vascular Endothelial growth factors (different isoforms of VEGF and PlGF) and their receptors (VEGF R1 and R2 receptors, angiopoïtin receptors and neuropilin) are major components of the regulatory machinary that govern vascularization. Among proteases involved in tissue remodelling, are at least the plasminogen system ( plasminogen activators -tPA, uPA- , their inhibitor PAI-1), matrix metalloproteinases (MMPs) and related proteinases, the ADAMs ("a disintegrin and metalloproteinases"). They degrade extracellular matrix components, but also other proteins such as growth factors, cytokines/chemokynes, their receptors, growth factor binding proteins, integrins and cell adhesion molecules (cadherin and CD44).

To unravel the molecular mechanisms underlying physiological and pathological angiogenesis, pharmacological and genetic approaches are used. Different in vivo and in vitro models including transplantation of malignant cells into mice, subretinal choroidal angiogenesis induced by laser photocoagulation, aortic ring assay, in vitro migration assay and lymphatic ring assay. These models are applied to transgenic mice (Knock-out mice) deleted for genes of angiogenic factor (VEGF,PlGF), MMP or serine protease families. These models are usefull to evaluate inhibitors of MMPs or antagonists of angiogenic factors. Expression and localisation of chemokines/cytokines, proteases, their inhibitors, cell surface receptors (receptors for VEGF, integrins, proteases) are determined by ELISA, RT-PCR, Western blotting on total tissue extracts or on cell islets isolated by laser capture microdissection on tissue sections. Computerized image analysis are used for objective and automatic quantification.
Our study is focused on tissue remodelling associated to:

- physiological event :embryonic implantation and

- pathological conditions characterized by:

an excess of angiogenesis: cancer (breast, cervical, endometrial and lung cancer), age related macular degeneration (AMD) and endometriosis.

a defect of angiogenesis: preeclampsia

an abnormal inflammation : asthma