Biomedical Engineering Reference
In-Depth Information
• In particular, independent from its deleterious functions in lipid
metabolism, apoC-III, alone or as a component of triglyceride-rich
lipoproteins, activates pro-inl ammatory and pro-atherogenic pathways in
monocytes and endothelial cells, leading to endothelial dysfunction and
enhanced monocyte adhesion
(Fig. 6)
.
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Fig. 6
h e pleiotropic actions of apoC-III that may contribute to atherogenesis. ApoC-III
is a major component of TG-rich lipoproteins (VLDL, chylomicrons) and HDL. ApoC-III
delays TG-rich lipoprotein clearance and uptake by the liver and enhances VLDL synthesis and
secretion. As such, apoC-III is a major modulator of TG-rich lipoprotein metabolism. ApoC-III
is also a major constituent of HDL, and our results suggest HDL CIII+ lose the anti-adhesion
function of HDL CIII-. Recent studies by us and others showed that apoC-III increases adhesion
molecule expression and decreases NO production in endothelial cells and consequently
results in endothelial dysfunction and enhances vasoconstriction. ApoC-III also promotes pro-
inl ammatory actions by activating NF-κB and inducing β1-integrin expression in monocytes that
leads to enhanced adhesion to endothelial cells. ApoC-III may also induce cytokine expression
in macrophages and promote foam-cell formation. h ese multiple apoC-III-mediated ef ects
may independently contribute to enhance the risk of cardiovascular diseases. Reproduced from
Kawakami
et al.
(2008a) with permission.
• Elevated plasma apoC-III is a common phenotype in patients with
hypertriglyceridemia, insulin resistance or obesity, subjects who are also at
increased risk for cardiovascular disease.
