Development of animal model of hyperlipidemia related to evolution of coronary artery disease.

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We segregated from WHHL (Watanabe heritable hyperlipidemic) rabbits two strains with high and low levels of hypertriglyceridemia. Selected inbreeding was repeated on the level of plasma triglycerides. Penetrance of a low level (triglyceride<500mg/dl ; TGL group) and a high level (triglyceride>=500mg/dl ; TGH group) of hypertriglyceridemia was 100% and 90% at the 4th generation, respectively. Plasma total cholesterol and triglycerides, measured enzymatically, were 719 <plus-minus> 131 (mean <plus-minus> SD) and 241 <plus-minus> 69mg/dl, respectively in TGL group (9-10 month old rabbits ; n=14) and those in TGH group (other 9-10 month old rabbits ; n=12) were 1239 <plus-minus> 410 (p<0.01 vs TGL group) and 1912 <plus-minus> 1256mg/dl, (p<0.01 vs TGL group), respectively. The lipoproteincholesterol level in the TGH group was linearly related to the total plasma levels of triglyceride (r=0.931, p<0.01) and VLDL-cholesterol (r=0.952, p<0.01). In the TGL group, total cholesterol level was linearly related to LDL-cholesterol (r=0.977, p<0.01), but not to VLDL-cholesterol. Lipoprotein profile of TGH rabbits differed from those of TGL rabbits with regard to the variation of lipoprotein particle size as well as to the relation between LDL-and VLDL-cholesterol. The severity of hypertriglyceridemia was determined by the amount of VLDL cholesterol. Accordingly, the present animal models of heritable hypertriglyceridemia associated with hypercholesterolemia will provide important animal models in genetic, metabolic and pathophysiological analyzes of hyper