Lipoprotein Metabolism And Activity Of Protein Structure And Function

Hypertriglyceridemia (HTG) is an important independent risk factor for coronary artery disease (CAD). It is an integral component of the overlapping syndromes of central obesity, insulin resistance, and atherogenic lipoprotein profile (elevated levels of triglyceride, reduced levels of HDL, and the dense and small LDL pattern).ApoAV is located about 27kb upstream of the well-characterized APOA1/APOC3/APOA4 gene-cluster, and encodes the newest member of the apolipoprotein family, apolipoprotein AV (apoAV). Over-expression of human ApoAV in transgenic mice or adenoviral vector-mediated transfer of ApoAV into mice produced a 60-70% decrease in plasma TG levels, whereas ApoAV knockout micehave 4-fold higher plasma TG levels than controls. ApoAV-deficiericy is associated with severe HTG in humans. These data indicate that apoAV plays an important role in the regulation of TG metabolism. However, the exact molecular mechanism underlying the association between apoAV and TG levels remains unclear. Both a decreased hepatic secretion of VLDL and/or an increased catabolism of TG-riched lipoproteins (TGRLs) may be involved.LPL-dificient and ApoE-dificient mice are two useful models for studying lipoprotein metabolism and HTG pathogenesis. Homozygous LPL-dificient mouse, lacking almost complete LPL activity, is a model of hyperchylomicronemia (type I hyperlipidemia). ApoE-deficient mouse, lacking the natural ligand for the LDL receptor (LDL-R) and LDL-R related protein (LRP), develops a combination of severe hypercholesterolemia and mild HTG (type III hyperlipidemia).Although there is precedent for the lipid-lowering action of apoAV in the wildtype mice, the effect of apoAV has not been systemically studied in the HTG...