Biomedical Engineering Reference
In-Depth Information
of vascular adhesion molecule activation. However, the direct contribution of
apoA-I, the main structural protein of HDL, in these actions remains obscure.
HDL inhibit cytokine-induced expression of VCAM-1, ICAM-1 and E-selectin
in vascular EC, but this ef ect strongly depends on the phospholipid composition
of HDL as the inhibitory ef ects are not exerted by lipid-free apoA-I or apoA-II
(Nofer
et al.
2003). On the other hand, a recent study demonstrates that lipid-
free apoA-I can inhibit expression of integrin CD11b on monocytes in a process
mediated by ABC-A1 (Murphy
et al.
2008). In addition, apoA-I induces TGF-β2,
an anti-inl ammatory modulator, in vascular EC (Norata
et al.
2005). h ese data
suggest an anti-inl ammatory role of apoA-I in EC and monocytes.
CONCLUSIONS
h ese recent studies by our group and others suggest that apolipoproteins, the
dominant protein moieties of circulating lipoproteins, have two-fold functions.
First, apolipoproteins are crucial regulators of lipoprotein homeostasis, and
their dysmetabolism underlies the pathogenesis of many lipid disorders. Second,
apolipoproteins directly interact with vascular cells and exert either pro- or anti-
atherogenic ef ects. h is dual role makes apolipoproteins attractive targets for
pharmacological intervention of lipid disorders and coronary heart disease. In
particular, our results suggest that apoC-III, alone or as a component of triglyceride-
rich lipoproteins, activates monocytes and vascular EC, enhancing adhesion. Taken
together with apoC-III's established function in hypertriglyceridemia, lowering
or modulating apoC-III may not only improve lipid proi le but also prevent the
development of inl amed atherosclerotic plaques, opening a new dimension in
lipoprotein research.
SUMMARY
• Mechanisms responsible for atherosclerotic lesion development have
largely focused on the accumulation and retention of LDL in the arterial
intima and their subsequent oxidative modii cation.
• h e oxidation leads to activation of the endothelium and, in particular,
expression of cell adhesion molecules that mediate leukocyte adherence.
• Recent novel i ndings by us and others that apolipoproteins, protein
constituents of circulating lipoproteins, induce adhesion molecules provide
another direct link between dyslipidemia and atherogenesis.
• Among these lipoproteins, apoC-III and Lp(a) induce expression of
adhesion molecules in monocytes and vascular EC, whereas apoE and
apoA-I seem to suppress it.
