Apolipoproteins and Cell Adhesion Molecules - Adhesion Molecules - page 432

Fig. 2 Apolipoprotein C-III regulates plasma lipoprotein metabolism by multiple mechanisms.
LpL, lipoprotein lipase; HL, hepatic lipase; LDL-R, LDL receptor.
stimulates hepatic VLDL assembly and secretion (Sundaram et al. 2007, Zheng
et al. 2007).
Clinical evidence from us and others has demonstrated the importance of
apoC-III as a predictor of cardiovascular disease outcomes (Lee et al. 2003, Sacks
et al. 2000). h e Cholesterol and Recurrent Events (CARE) trial demonstrated
that plasma concentration of apoC-III in apoB lipoproteins (VLDL and LDL)
is a strong, independent risk factor for recurrent coronary heart disease (Sacks
et al. 2000) (Fig. 3A) . In a substudy of the CARE trial, the concentration of LDL
particles containing apoC-III was the strongest lipoprotein predictor of risk for
recurrent cardiovascular events in type 2 diabetic patients (Lee et al. 2003) (Fig.
3B) . Since the concentration of LDL containing apoC-III is much lower than the
majority of plasma LDL that does not have apoC-III, and in view of the large risk
associated with these relatively small increments of concentration of LDL with
apoC-III, we hypothesized that apoC-III possesses direct atherogenic properties
in addition to its deleterious ef ects on lipoprotein metabolism.
Following this thinking, we and Dr. Yoshida's group have systematically
investigated direct pro-inl ammatory and pro-atherogenic ef ects of apoC-III on
vascular cells, demonstrating that this apolipoprotein, alone or as a component
of plasma apoB lipoproteins, promotes EC and monocyte activation and their
adhesion. Figure 4 summarizes our current understanding of these pleiotropic
ef ects of apoC-III.