Biomedical Engineering Reference
In-Depth Information
ApoE
ApoE, a 34-kDa glycoprotein, circulates in plasma in association with various
lipoproteins, including chylomicrons, VLDL, IDL and HDL. In addition to its well-
known regulatory functions in lipid metabolism, apoE may also possess direct
anti-atherosclerotic ef ects on vascular cells. For example, apoE-dei cient mice
exhibited elevated VCAM-1 and ICAM-1 levels in the vessel wall and aortic lesions
(Nakashima
et al.
1998), an ef 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-dei cient
mice normalized the LPS-induced plasma protein levels of
IL-12 p40, indicating that apoE may suppress the type I inl ammatory response
(Ali
et al.
2005). ApoE also suppresses cytokine-induced VCAM-1 expression in
human EC (Stannard
et al.
2001). h 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 ef 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.
LIPOPROTEIN(a)
Plasma Lp(a) represents a major risk factor for premature coronary heart
disease in patients with concomitant hypercholesterolemia. Lp(a) may promote
atherosclerosis at least in part through induction of adhesion molecules in vascular
EC. Lp(a) activates EC expression of VCAM-1 and E-selectin and ICAM-1 (Takami
et al.
1998), and also induces secretion of monocyte chemotactic protein (Gosling
et al.
1999). h e exact mechanism behind Lp(a)-induced ICAM-1 activation
remains incompletely understood, but it may account for TGF-β inhibition
(Takami
et al.
1998). Lp(a) also directly interacts with β2-integrin Mac-1, thereby
promoting monocyte adhesion and transendothelial migration (Sotiriou
et al.
2006). In addition, elevated Lp(a) levels are associate with impaired endothelium-
dependent vasodilation in coronary arteries (Tsurumi
et al.
1995), indicating a
role of Lp(a) in inhibition of NO and endothelial dysfunction.
ApoA-I
Epidemiological studies have i rmly established an inverse relationship between
plasma HDL levels and risk of coronary heart disease. In addition to reverse
cholesterol transport, a process of removing excess cholesterol from peripheral cells,
HDL also exhibit direct antioxidant and anti-inl ammatory properties on vascular
cells. h ese pleiotropic atheroprotective functions of HDL include suppression
