VEGFA and neoplasm: We know that, in addition to VPF or VEGF, many other vascular mediators can further enhance the EPR effect, including ATII, BK, NO, peroxynitrite (ONOO2), matrix metalloproteinases (MMPs, or collagenase) and PGs.16,17 The smooth muscle layer of tumor blood vessels is absent, which makes them unable to sense neurotransmitters and contract.