Observations with Radioactive Hydrogen (H ³ ) in Experimental Atherosclerosis

Abstract

Tritium has been used to study certain aspects of endogenous and exogenous cholesterol metabolism in normal and hypercholesterolemic rabbits. Special attention is given to turnover studies on aortic cholesterol. Labeled cholesterol has been used for feeding experiments an(l the subsequent rise of serum cholesterol specific activity has been investigated.G OFMAN and co-workers' have made observations on the mode of transport of cholesterol in lipoprotein molecules in serum, and have presented evidence to link the appearance of certain of these lipoprotein molecules in human serum with the development of atherosclerosis. A general study of these molecules has been undertaken in this laboratory, directed toward gaining a fuller knowledge of their origin, function and fate, and thus clarifying their position in the pathogenesis of atherosclerosis. Cholesterol metabolism necessarily occupies a position of prominence in this study. Lipoprotein molecules similar to those occurring in human serum are to be found in great concentration in the hypercholesterolemic rabbit laying down atheromas, and for this reason the rabbit has been selected for this preliminary study. This report will present some observations on the fate of exogenous and endogenous cholesterol in normal and hypercholesterolemic rabbits.Rittenberg and Schoenheimer2 showed that in vivo cholesterol synthesis incorporates hydrogen from the body water into the cholesterol molecule, and Bloch and Rittenberg3 prepared deuterium-labeled cholesterol. Thus an opportunity to study certain aspects of endogenous and exogenous cholesterol metabolism is afforded. Tritium has been used in this work for the hydrogen label; tritium-labeled cholesterol was prepared4 using the method of From the Donner

Studies on the mechanism of action of unsaturated fats on cholesterol metabolism in the rabbit.

“…These results are in agreement with the findings of Spritz, Ahrens, and Grundy (15) (19). The turnover time in the present studies for rabbit serum cholesterol was longer (average 25.4 days) than has previously been reported (30). This difference is probably due to the fact that our studies were carried out over a very long period of time in order to be certain that the specific activity declined at an exponential rate.…”

Observations Concerning the Production and Excretion of Cholesterol in Mammals

“…However, qualitative changes occur in the blood cholesterol, since as has been shown by Biggs et al (12), ingested labelled cholesterol quickly interchanges with blood cholesterol. More recently also, Page et al (26), have demonstrated that the lipoproteins of intestinal lymph change following ingestion of cholesterol and with the drainage of such lipoproteins into the blood stream it seems most likely that for a while at least, the plasma cholesterol is altered qualitatively.…”

Rate of Cholesterol Synthesis in Hypo- And Hyperthyroid Rats

“…The non-saponifiable material was extracted with ether. The cholesterol was precipitated with digitonin and the specific activity determined as described previously (9,10).…”