The effect of polyunsaturated fats on bile acid metabolism and cholelithiasis in squirrel monkeys.

Squirrel monkeys (Saimiri sciureus) were fed diets containing safflower oil, butter, or coconut oil and 1 mg cholesterol/cal for 15--17 mo to examine the effect of type of fat on cholelithiasis and bile acid metabolism. Controls were fed low cholesterol diets containing an isocaloric mixture of the three fats. Cholic acid fractional catabolic rate, pool size, chenodeoxycholic acid pool size, and total bile acid pool size and excretion rate were estimated using a modification of Lindstedt's isotopic turnover procedure. The animals fed the safflower oil diet had the highest incidence of cholelithiasis (9/10) when compared to those fed butter (3/7) and coconut oil (1/7). Animals consuming the low cholesterol control diet did not develop gallstones. The butter- and coconut oil-fed groups had significantly (p less than 0.05) expanded bile acid pools when compared to controls, and the butter-fed group had a significantly increased (p less than 0.05) cholic acid fractional catabolic rate. The safflower oil group had the smallest mean bile acid pool and the highest mean lithogenic index of the cholesterol-fed groups. It was concluded that the safflower oil-fed animals had a higher incidence of cholelithiasis than the butter group because, unlike the latter group, they did not compensate for a high cholesterol intake by stimulating bile acid synthesis. The animals consuming coconut oil apparently did not absorb cholesterol to the extent of the other groups and as a result their bile did not become saturated with cholesterol.

The effect of arylsulfonate esters on cholesterol--aggravated atherosclerosis in White Carneau Pigeons.

The arylsulfonate esters of linoleyl, stearyl, and decyl alcohols were found to reduce significantly the accumulation of cholesterol in the plasma and livers of White Carneau pigeons subjected to a diet of Purina pigeon pellets coated with 0.25% cholesterol and 10% lard when fed for periods ranging from 9--12 months; no effects were observed in normocholesterolemic pigeons. These compounds produced no toxic side effects and were found to significantly attenuate the development of aortic atherosclerosis. The effect on aortic atherosclerosis was most likely the result of the lowering of plasma cholesterol concentrations. Linoleyl p-toluenesulfonate appeared to be the most effective of the three arylsulfonates tested, both with respect to the reduction of plasma and liver cholesterol accumulation and attenuation of the atherosclerotic process.

Hyperlipidemia, hypercoagulability, and accelerated thrombosis: studies in congenitally hyperlipidemic rats and in rats and monkeys with induced hyperlipidemia.

Inbred Carworth Farms Nelson (CFN) congenitally hyperlipidemic rats had significantly shorter coagulation and prothrombin times and higher levels of coagulation factors, II, V, VII, VIII, and X than did controls. Conversely, congenitally hypolipidemic rats of the same strain had significantly longer coagulation and prothrombin times and lower levels of factors II, V, VII, X and XII and of blood platelets than did controls. A loop-shaped polyethylene cannula was inserted into the aorta to assess the potential for thrombosis. The hyperlipidemic group obstructed this significantly faster and the hypolipidemic group slower than did the controls. Normal CFN rats made hypertensive by unilateral renal artery clip developed hypertension together with significantly elevated serum cholesterol and factor VII and X levels. Rhesus monkeys with diet-induced hyperlipidemia showed shorter prothrombin times and higher factor X levels than did controls on normal diet. By selective breeding, two groups of squirrel monkeys were obtained. Both groups had similar serum cholesterol levels on a normal diet but one group (hyperresponders) showed higher serum cholesterol levels on a cholesterol-containing diet than did the other (hyporesponder) group. Both groups showed significantly elevated levels of factors II, V, VII, IX and X on a cholesterol-containing diet. There was good correlation between the levels of many coagulation factors and serum cholesterol in both rats and monkeys. If thrombosis is important in the genesis of atherosclerosis, these findings could indicate that elevation of plasma lipids may play a role, via the coagulation pathway, in the production of human vascular disease.

Proline hydroxylase activity and collagen content of pigeon aortas with naturally-occurring and cholesterol-aggravated atherosclerosis.

Proline hydroxylase activity and collagen content were determined in atherosclerotic plaque, fatty streak, and normal tissue from aortas of White Carneau pigeons with naturally-occurring of cholesterol-aggravated atherosclerosis. Little increase in collagen content or proline hydroxylase activity occurred in fatty streaks or plaques from birds with cholesterol-aggravated atherosclerosis. This is consistent with the morphologic observation of the presence of little or no "fibromuscular cap" in these cholesterol-aggravated lesions. Both normal and plaque tissue from arotas of birds with naturally-occurring atherosclerosis contained more collagen than did similar tissues from control birds or birds with cholesterol-aggravated lesions. The largest proportion of this increase in collagen content probably represented an age effect since it occurred in normal as well as atherosclerotic tissue. Plaques from aortas of birds with naturally-occurring atherosclerosis did contain, however, significantly more collagen than normal tissue from the same aortas. This is consistent with the presence of a prominent "fibromuscular cap" in these naturally-occurring lesions. Proline hydroxylase activity was less in these lesions than in normal tissue from the same aortas. Consequently increased proline hydroxylase activity and collagen content are not greatly altered in association with development of cholesterol-aggravated atherosclerotic lesions in pigeons. On the other hand, well-developed naturally-occurring lesions contained increased concentrations of collagen but showed no increase proline hydroxylase activity. This is not to say though, that active collagen synthesis and presukably increased proline hydroxylase activity did not take place at some point in the development of these naturally-occurring lesions.