Abstract
A new and exciting animal model for endogenous hypercholesterolemia has recently become available through the discovery of a strain of rabbits designated as Watanabe heritable hyperlipidemic (WHHL). In these animals, massive hypercholesterolemia results from a single genetic defect of LDL receptor, and severe atherosclerosis occurs despite the ingestion of a cholesterol-free diet. In comparison with values in healthy normal-weight normolipidemic rabbits, activities of vitamin K-dependent clotting factors, clotting factors of contact phase, clotting factor VIII activity (F VIII: C), and fibrinogen were found to be significantly higher in WHHL rabbits. These data suggest hypercoagulable state in WHHL rabbit. Furthermore, it is known that atherosclerosis of the aorta severely develops in ranging from 5 to 15 months of age, and coronary disease begins to develop at 5 months of age. Vitamin K-dependent cloting factors were already higher at 2 months of age in the WHHL rabbits, and were not increased in amounts with age. Clotting factors of contact phase and fibrinogen had increased at the age 5 and 8 months. In WHHL rabbits, F VIII: C had increased during these months and then decreased. However, such changes in F VIII: C were not seen in control rabbits. Clotting factors might increase in hyperlipemia and some clotting factors would change in degree with development of atherosclerosis.
