EFFECTS OF VITAMIN-K-2 (MENATETRENONE) ON ATHEROSCLEROSIS AND BLOOD-COAGULATION IN HYPERCHOLESTEROLEMIC RABBITS

gamma-Carboxyglutamic acid (Gla)-containing protein, synthesized in th e presence of vitamin K, has been found in atherogenic plaques, but th e pharmacological effect of vitamin K on atherosclerosis is unclear. W e examined whether vitamin K-2 (menatetrenone) could affect the progre ssion of both atherosclerosis and hypercoagulability in hypercholester olemic rabbits. Vitamin K-2 in daily doses of 1, 10 and 100 mg/kg was given with a 0.5% cholesterol diet for 10 weeks to 8 rabbits each. The plasma levels of total-cholesterol in the vitamin Ka-treated groups w ere clearly lower than that of the hypercholesterolemic control group. The excessive dose of vitamin K-2, even at the high dose of 100 mg/kg /day for 10 weeks, did not accelerate the progression of atheroscleros is and did not promote the coagulative tendency in the rabbits. In con trast, the vitamin K-2 treatment (1 to 10 mg/kg/day) suppressed the pr ogression of atherosclerotic plaques, intima-thickening and pulmonary atherosclerosis, the increase of ester-cholesterol deposition in the a orta, and both the elevation in plasma factor X level and increase in Hepaplastin(R)test value in the rabbits. These results indicate that t he pharmacological dose of vitamin K-2 prevents both the progression o f atherosclerosis and the coagulative tendency by reducing the total-c holesterol, lipid peroxidation and factor X activity in plasma, and th e ester-cholesterol deposition in the aorta in hypercholesterolemic ra bbits.