Quiescent endothelial cells (ECs) are in intimate contact with pericytes and smooth muscle cells (SMCs). Vascular stability and integrity is maintained by constitutive Ang-1/Tie2 signaling (left side). Ang-1 clusters Tie2 receptors at endothelial cell junctions.2 Upon activation, ECs normally release their endogenously stored Ang-2 pools from Weibel-Palade bodies. Ang-2 activates ECs by competition with the homeostatic Ang-1 for binding to their common EC receptor, Tie2. CLL cells also can release Ang-2 and thereby induce EC activation and angiogenesis.