A review of the role of apolipoprotein C-II in lipoprotein metabolism and cardiovascular disease

Metabolism. 2012 Jul;61(7):906-21. doi: 10.1016/j.metabol.2011.12.002. Epub 2012 Feb 2.

Abstract

The focus of this review is on the role of apolipoprotein C-II (apoC-II) in lipoprotein metabolism and the potential effects on the risk of cardiovascular disease (CVD). We searched PubMed/Scopus for articles regarding apoC-II and its role in lipoprotein metabolism and the risk of CVD. Apolipoprotein C-II is a constituent of chylomicrons, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein (HDL). Apolipoprotein C-II contains 3 amphipathic α-helices. The lipid-binding domain of apoC-II is located in the N-terminal, whereas the C-terminal helix of apoC-II is responsible for the interaction with lipoprotein lipase (LPL). At intermediate concentrations (approximately 4 mg/dL) and in normolipidemic subjects, apoC-II activates LPL. In contrast, both an excess and a deficiency of apoC-II are associated with reduced LPL activity and hypertriglyceridemia. Furthermore, excess apoC-II has been associated with increased triglyceride-rich particles and alterations in HDL particle distribution, factors that may increase the risk of CVD. However, there is not enough current evidence to clarify whether increased apoC-II causes hypertriglyceridemia or is an epiphenomenon reflecting hypertriglyceridemia. A number of pharmaceutical interventions, including statins, fibrates, ezetimibe, nicotinic acid, and orlistat, have been shown to reduce the increased apoC-II concentrations. An excess of apoC-II is associated with increased triglyceride-rich particles and alterations in HDL particle distribution. However, prospective trials are needed to assess if apoC-II is a CVD marker or a risk factor in high-risk patients.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticholesteremic Agents / therapeutic use
  • Apolipoprotein C-II / blood
  • Apolipoprotein C-II / genetics
  • Apolipoprotein C-II / metabolism*
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / prevention & control
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / metabolism
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / metabolism
  • Lipoproteins / metabolism*
  • Male
  • Mice
  • Mutation
  • Rats

Substances

  • Anticholesteremic Agents
  • Apolipoprotein C-II
  • Lipoproteins