Matrix metalloproteinases in Angiogenesis and Inflammation

The vasculature is responsible for the optimal distribution of nutrients and oxygen throughout the body and must therefore continuously adapt to the changing needs of the tissues. To do this, vascular networks must be remodeled, eliminating (by pruning) or expanding (by duplication) segments with too little or too much blood flow. Blood flow also regulates immune system cells by favoring their free movement and their contact, homing, firm adhesion or endothelial transmigration in different contexts. Our group has been working for years to elucidate the cellular basis and molecular mechanisms that govern vascular and immune responses during inflammation and how they may contribute to tissue repair. To this end, we have focused on the actions of membrane-anchored extracellular matrix metalloproteinases (MT-MMPs), a subfamily of proteases that can dynamically modify the extracellular matrix and the activity of membrane or soluble proteins, and in particular their impact on the behavior of endothelial cells as well as monocytes/macrophages. We are currently focused on delving into the actions of blood flow, MT-MMPs and new players in the remodeling of vascular networks and the intravascular crawling of patrolling monocytes, a subpopulation responsible for monitoring the integrity of the endothelium and combating foreign agents. To this end, we have developed innovative techniques for advanced microscopy and 3D image analysis, computational tools, in vitro flow assays and in vivo reporter mouse models. Our lines of research will improve the understanding of these processes and allow us to identify targets to: i) improve capillary perfusion and tissue repair in cardiovascular or inflammatory pathologies; and ii) boost immune activity to fight infections and tumor metastasis mainly in the lung.