Another possible mechanism of atheroprotection by the Tie2-Scarb1 transgene may relate to the known bioactive signaling molecule sphingosine 1-phosphate, which participates in many cardiovascular effects of HDL, including reduction of VCAM-1 and ICAM-1 expression by EC and protection against atherosclerosis (see review [40]). This evidence concerns the gene ICAM1 and atherosclerosis.