Regulating the regulators of angiogenesis by CCN1 and taking it up a Notch

CCN1 is encoded by an extracellular matrix protein-gene that is essential for the proper development of the cardiovascular system and the control of angiogenesis, inflammation, progenitor cell lineage commitment and extracellular matrix protein remodeling during the adult life. High-precision genetic models of tissue-specific gene deletion demonstrated a pivotal role of CCN1 in providing positional information to angiogenic endothelial cells (ECs) during the outgrowth and maturation of nascent blood vessel sprouts, fine-controlling Notch-dependent inter-endothelial cell communications and mediating interaction with inflammatory cells. Some of these pleiotropic activities of CCN1 are unique among proteins of the extracellular matrix. Thus, CCN1 represents a model molecule for investigating and unraveling novel aspects of extracellular protein signaling in vascular development and diseases.