High-density lipoproteins animal models

Mice and other animal models of disease are often poor mimics of the human condition. However, the expression of human genes in these animals can initiate development of the disease. In mice, the distribution of cholesterol between low-density lipoproteins (LDL) and high-density lipoproteins (HDL) is quite distinct from that in humans. However, if the human enzyme, cholesterol ester transfer protein (CETP) is expressed in mice, the ratio of LDL HDL becomes more human in profile. Inhibition of CETP is a target for antiatherosclerotic drags and there now exists an animal model in which to test them. 

VLDL is metabolized via intermediate density lipoprotein (IDL) to LDL in the plasma by the action of lipoprotein lipase [72], Hepatic lipase may also contribute to the formation of TG-rich LDL particles [73], The increased production/decreased clearance of VLDL also may result in the increased production of precursors of small dense LDL (sd-LDL) particles [57,74,75], Such sd-LDL particles have been shown to contribnte to vascnlar diseases, as LDL receptors have a reduced affinity for sd-LDL, and sd-LDL are more vulnerable to oxidative modification [76-78], Numerous clinical stndies have shown increased CVD in subjects with high prevalence of sd-LDL [79], In animal models and in human diabetic conditions, sd-LDL levels are elevated [80,81] and snch accumulation appears to be accompanied by decreased paraoxonase 1 (PONl) activity. PONs are antioxidant enzymes that are known to detoxify H2O2 and lipid peroxides [82,83], The presence of PONl in lipoproteins also protects the... 

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