The circle of arteriogenesis. Upon occlusion of a feeding artery, blood flow is redirected in preexisting collaterals circumventing the stenosed artery. Because of the increased blood flow, collaterals experience increased shear stress, which results in release of RNA from ECs. eRNA acts as mechanotransducer provoking EC activation. Activated ECs release VWF from their WPBs, which activates platelets to form PNAs. These, in turn, are essential for mast cell activation, which is a prerequisite for the recruitment of leukocytes that boost vascular cell proliferation and, hence, vessel growth by supplying growth factors and cytokines. When collaterals reached a critical size, allowing them to substitute for the function of the occluded artery, blood flow is normalized, and the collaterals cease to grow.