ApoC-III has central role in pathogenesis of hypertriglyceridemia
MedWire News: Apolipoprotein (apo)C-III plays a central role in the metabolic defects in very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) seen in hypertriglyceridemia, US scientists have demonstrated.
The findings support a direct link between hypertriglyceridemia and coronary heart disease (CHD) and suggest that apoC-III may be a potential therapeutic target in dyslipidemia, vascular disease, and thrombosis.
Frank Sacks (Harvard School of Public Health, Boston, Massachusetts) and co-workers have previously shown that apoC-III and apoE – surface protein components of VLDL and LDL – play a dominant role in regulating the metabolism of these lipoproteins.
In this study, they used stable isotope labeling to study the kinetics of apoB, which is the principle protein component of apoC-III, in nine patients with moderate hypertriglyceridemia and 12 normotriglyceridemic control individuals.
Their study, which is reported in the journal Circulation, found that hypertriglyceridemic patients had a three-fold higher hepatic secretion of apoC-III-rich VLDL and a 50% lower secretion of VLDL expressing both apoC-III and apoE, compared with controls.
This abnormal VLDL secretion pattern resulted in a 39% reduction in clearance of light VLDL, a change that is compatible with the antagonizing effects of apoC-III on apoE-induced clearance of triglyceride-rich lipoproteins, according to the researchers.
They also showed that apoC-III contributes to the formation of dense LDL phenotype; this occurred via four distinct mechanisms, which the team terms a “quartet of kinetic perturbations.”
Taken together, the results indicate “that the action of apoC-III to retard clearance of triglyceride-rich lipoproteins is a central metabolic feature underlying major changes in VLDL and LDL metabolism in hypertriglyceridemia,” Sacks et al write.
These adverse changes in apoB lipoprotein metabolism caused by apoC-III, in addition to the recently established pro-atherogenic effects of apoC-III itself, “directly link moderate hypertriglyceridemia to increased risk for CHD,” they believe.
The researchers add: “Modulating apoC-III may not only improve lipid profiles but also prevent the development of atherosclerotic plaques and their acute thrombotic complications.”
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By Joanna Lyford