Angiogenèse et morphogenèse de l'arbre vasculaire : de la biologie cellulaire à la clinique.

Abstract

L'angiogenèse, c'est-à-dire la formation de nouveaux vaisseaux sanguins, est essentielle pour la croissance et l'homéostasie. Ce processus implique le mouvement et la différenciation de cellules endothéliales et non endothéliales (péricytes, cellules musculaires lisses), dont le résultat final est la morphogenèse d'un arbre vasculaire complexe et multifonctionnel. La compréhension des mécanismes de base de ce processus au niveau moléculaire a permis de réévaluer leur rôle dans la pathogénie de plusieurs maladies, par exemple la croissance tumorale, les rétinopathies et les malformations vasculaires telles que les angiomes. Par ailleurs, la compréhension de phénomènes physiologiques, tels que la réparation tissulaire, la fertilité (modification de la muqueuse utérine, ovulation, croissance du corps jaune) et la formation de vaisseaux collatéraux en cas d'ischémie, a aussi bénéficié de ces nouvelles connaissances. Ainsi, l'angiogenèse représente, par excellence, un domaine de transfert rapide de connaissances entre science fondamentale et médecine clinique.

Angiogenesis is a necessary requirement for the growth of normal and neoplastic tissues. Immature endothelial-lined tubes which arise during angiogenesis differentiate into capillaries or larger vessels such as arteries and veins. Interest in these processes has gained impetus recently with the identification of novel mediators and their associated receptor tyrosine kinases. The early phase of angiogenesis includes endothelial cell migration, proliferation and extracellular proteolysis, and is mediated in part by the vascular endothelial growth factor (VEGF) family. Reciprocal interactions then occur between pluripotent mesenchyma and endothelium, resulting in the differentiation of pericytes and smooth muscle cells. These interactions are mediated by the transforming growth factor-b (TGF-b), platelet-derived growth factor (PDGF) and angiopoietin families. Fibroblast growth factors (FGF) have long been implicated in the regulation of angiogenesis. Although a large body of evidence gained principally from gene deletion studies questions their role during development, a role during inflammatory and tumor angiogenesis cannot be excluded. A novel role in angiogenesis as well as specification of arterial and venous vascular segments has recently been attributed to certain members of the Ephrin family. Advances in our understanding of the mechanisms of angiogenesis, together with the accumulation of information on processes as diverse as postnatal growth, wound healing and tissue repair, tumorigenesis, diabetic retinopathy, fertility/sterility and vascular malformations, has provided new hope for novel therapeutic strategies.