ABSTRACT
ApoE, a 34-kDa glycoprotein, circulates in plasma in association with various lipoproteins, including chylomicrons, VLDL, IDL and HDL. In addition to its wellknown regulatory functions in lipid metabolism, apoE may also possess direct anti-atherosclerotic eff ects on vascular cells. For example, apoE-defi cient mice exhibited elevated VCAM-1 and ICAM-1 levels in the vessel wall and aortic lesions (Nakashima et al. 1998), an eff ect that could be corrected by transgenic expression of low levels of apoE (Ma et al. 2008) or bone marrow transplantation from normal mice (Linton et al. 1995). Furthermore, reconstitution of apoE expression in the liver of apoE-defi cientmice normalized the LPS-induced plasma protein levels of IL-12 p40, indicating that apoE may suppress the type I infl ammatory response (Ali et al. 2005). ApoE also suppresses cytokine-induced VCAM-1 expression in human EC (Stannard et al. 2001). Th e suppression of endothelial activation by apoE most likely occurs via stimulation of eNOS; apoE increased levels of intracellular NO and its surrogate marker, cyclic guanosine monophosphate, while the eNOS inhibitor, ethyl-isothiourea, blocked its eff ect (Stannard et al. 2001). It is possible that apoE receptor 2 (apoER2), a member of the LDL receptor family, mediates apoE’s activation of eNOS.
