Activated ASMase converts sphingomyelin to ceramide in the outer plasma membrane and leads to formation of ceramide-rich macrodomains (CRMs), which serve as sites of stress-related specific multiprotein complexes and relay downstream apoptotic signaling [9, 36]. We showed that SDRT induced a rapid increase of the C16-ceramide (Table 1), which is the apoptogenic ceramide species, and Pazopanib synergistically increased the C16-ceramide level. The increase of C16-ceramide contributes to the reorganization of membrane rafts into large signaling platforms, CRMs, which affords a mechanism by which SDRT induces endothelial apoptosis and generates microvascular dysfunction. Recently, increasing studies using LC-MS to determine the changes in specific ceramide species revealed that C16-ceramide was preferentially associated with stress-induced apoptosis in a variety of cell types. C16-ceramide has also been shown to increase the sensitivity of Jurkat T cells and hepatocytes , and human chronic myelogenous leukemia (CML)  to Fas-mediated apoptosis. Increases in C16-ceramide levels in Jurkat cells occurred 2 h after initiation of apoptosis by ionizing radiation, whereas no change of C16-ceramide level was observed in RT-resistant cells. In the current study, C16-ceramide levels rapidly increased 2 min after SDRT and remained elevated for more than 10 min. The high radiosensitivity of BAEC may result from the 20–fold higher ASMase level in these cells as compared with other cells in the body. In addition to its crucial role in the formation of CRMs to mediate apoptotic signaling, C16-ceramide may also induce apoptosis by repression of pro-survival pathways. C16-Ceramide has been shown to activate ceramide-activated protein phosphatase leading to the dephosphorylation of p38 and Akt, which may negatively regulate the activities of downstream factors implicated in the regulation of apoptosis [27, 44].