Kelly McNagny and colleagues in a multilab study uncover mysteries of vascular lumen formation

The survival of mammals requires the formation of a complex network of blood vessels – tubes that are lined by endothelial cells – that traverse every organ, and dynamically respond to a range of pathophysiologic stresses. The blood vessels carry and regulate the delivery of essential factors including oxygen, nutrients and fluids, and dispose of unnecessary and damaging waste. Virtually every disease involves blood vessels, either as a primary cause of disease or as a victim of collateral damage. Understanding the mechanisms that underlie vasculogenesis (de novo formation of blood vessels) and angiogenesis (formation or sprouting of new vessels from pre-existing ones) is therefore critical for the design of novel therapeutic strategies for diseases such as cancer, arthritis, and myocardial ischemia.

Much effort has been exerted to determine how vascular tubes actually form. Indeed, studies from almost 100 years ago suggested that during vasculogenesis, lumens were formed from the coalescence of vacuoles within cells, i.e the cells “hollowed out”, and when situated end-to-end, formed a vessel. Until the work by Strilic et al in Developmental Cell, this was believed to be the primary mode of vasculogenesis. Through a multilab collaboration led by Eckhard Lammert in Germany, these investigators performed a comprehensive analysis of the formation of the mouse aorta, and demonstrated that endothelial cells initially organize into clumps or so-called “cords” that lack lumens. The endothelial cell-cell junctions within the cord gradually reposition to open up a space that widens to form a tube, through which blood may ultimately flow. Thus, the cord hollows, but the cells do not. Not only did these astute scientists morphologically define the steps of vascular lumen formation, but they also identified several critical cell biologic and biochemical events, defects of which might contribute to disease. In particular, the CD34-family of stem cell antigens, which the McNagny lab has shown to play a role in blocking adhesion, were found to be major players in hollowing and expansion of these lumens.

Get the whole story in Developmental Cell 2009; 17:505-515

Comments are closed, but trackbacks and pingbacks are open.