An ABC of apolipoprotein C-III: a clinically useful new cardiovascular risk factor?
BACKGROUND
Hypertriglyceridaemia, commonly found in subjects with obesity and type 2 diabetes mellitus, is associated with increased risk of coronary heart disease (CHD). Apolipoprotein C-III (apoC-III) plays an important role in regulating the metabolism of triglyceride-rich lipoproteins (TRLs) and may provide a new approach to assessing hypertriglyceridaemia.


OBJECTIVE
We review the role of apoC-III in regulating TRL metabolism and address the potential importance of apoC-III in clinical practice.


CONCLUSIONS
Hypertriglyceridaemia is chiefly a consequence of alterations in the kinetics of TRLs, including overproduction and delayed clearance of very-low density lipoprotein (VLDL). ApoC-III is an inhibitor of lipoprotein lipase and of TRLs remnant uptake by hepatic lipoprotein receptors. Elevated apoC-III, usually resulting from hepatic overproduction of VLDL apoC-III, may cause accumulation of plasma TRLs leading to hypertriglyceridaemia. The results from recent observational studies demonstrate that apoC-III is a strong predictor of risk for CHD, but this chiefly relates to apoC-III in apoB-containing lipoproteins. Lifestyle and pharmacological intervention can correct hypertriglyceridaemia by a mechanism of action that regulates apoC-III transport.


CONCLUSIONS
Targeting apoC-III metabolism may therefore be an important, new therapeutic approach to managing dyslipidaemia and CHD risk in obesity, insulin resistance and type 2 diabetes mellitus. However, further work is required to establish the practical aspects of measuring apoC-III in routine laboratory service and the precise therapeutic targets for serum total apoC-III and/or apoC-III in apoB-containing lipoproteins. While showing much promise as a potentially useful cardiovascular risk factor, apoC-III is not yet ready for prime time use in clinical practice.
Chan
D C
DC
Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia.
Chen
M M
MM
Ooi
E M M
EM
Watts
G F
GF
D053305:Apolipoprotein C-III / Q000097:blood / Q000737:chemistry / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications*; D024821:Metabolic Syndrome / Q000097:blood; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D053305:Apolipoprotein C-III; D015415:Biomarkers; D014280:Triglycerides