Matrix metalloproteinases in Angiogenesis and Inflammation

The vasculature is in charge of optimally delivering nutrients and oxygen throughout the body, and for that, it must constantly adapt to varying tissue needs. Upon damage or ischemia, the vasculature responds by forming new capillaries from pre-existing ones (angiogenesis) and by flow-driven angioadaptation to promote vascularization. Vascular blood flow also regulates immune cells favoring their free circulation, tethering, crawling, firm adhesion or transmigration in different contexts. Our group has long dedicated to elucidate the cellular principles and molecular mechanisms that govern vascular and immune responses during inflammation and how these can contribute to tissue repair. For this, we have focused on the actions of membrane-type matrix metalloproteinases (MT-MMPs), a subfamily of proteases that can modify dynamically the extracellular matrix and the activity of soluble and membrane proteins, and particularly in their impact on the behavior of endothelial and smooth muscle cells, and of monocytes/macrophages. We have recently recognized that MT-MMPs participate in vascular network reshaping, vessel wall mechanics, and intravascular crawling of patrolling monocytes, a subset in charge of surveying endothelial integrity and combating foreign agents. Our current research lines will deepen our understanding on these blood-flow regulated processes and allow identifying targets to: i) improve capillary perfusion and tissue repair in pathologies such as inflammatory bowel disease and peripheral/cardiac ischemia; and ii) boost immune endogenous activities to combat infectious and tumor metastatic disease.