Rose Jones

Experimental atherosclerosis in rhesus monkeys: II. Cellular elements of proliferative lesions and possible role of cytoplasmic degeneration in pathogenesis as studied by electron microscopy

Abstract The proliferative (non-necrotic) lesions of experimental atherosclerosis in the rhesus monkeys reported here are similar to those of the human in that they are composed primarily of mature smooth muscle cells, most of them containing lipid. In addition, there were small numbers of primitive cells, fibroblast-like cells, and smooth muscle cells of apparent intermediate maturity. This variety of morphologic classes of cells appears to reflect maturation of smooth muscle cells within the intimal lesion. Accompanying these cells were cells tremendously distended with lipid that could not be identified as to their histogenesis. They were probably either distorted smooth muscle cells or macrophages. Many foci suggesting cellular degeneration were found scattered throughout the proliferative lesions, while only a few were found in stock-fed monkeys. The increased number of cells in the proliferative lesions showing degenerative changes were apparently the indirect or direct result of feeding high-fat diets. Whatever their cause, it is likely that these foci of intracellular degeneration enhanced the development of the intimal lesion by stimulating the cells to proliferate.

Short-term feeding of unsaturated versus saturated fat in the production of atherosclerosis in the rat☆

Abstract Complex diets containing either 40% peanut oil, corn oil, or butter were fed to weanling rats for 3 months. The rats fed the peanut oil-containing diets developed intimal spindle cell lesions similar in many respects to early human atherosclerotic lesions. Rats receiving the butter-containing diets developed foam cell lesions which do not resemble human atherosclerosis. Under electron microscopy the spindle cells were of the smooth muscle type. They appeared more undifferentiated than the smooth muscle cells seen in aortic lesions in rats fed butter-containing diets for 12 months in a previous experiment. The primitive nature of the cells in the present experiment may have been due to their age, their unsaturated fatty acid environment, or other factors. The difference in serum fatty acids was possibly an important factor determining the type of lesion produced, since both the peanut oil- and butter-fed rats had much the same degree of hyperlipemia as shown by similar serum cholesterol and triglyceride levels. Both the peanut oil- and butter-fed rats showed a sharp drop in the relative percentage of serum arachidonic acid, even though the peanut oil-fed group had excessively high levels of serum linoleates. The absolute level of serum arachidonic acid, however, changed very little.

Coronary arteries of children and young adults: A comparison of lipids and anatomic features in New Yorkers and East Africans☆

Abstract Lipid classes (including fatty acids), crude protein, and calcium were measured in the coronary arteries of a total of 246 New Yorkers and East Africans from stillborn to 39 years of age. In subjects stillborn to 19 years of age a histological comparison of the arteries in the two groups was made. 1. (1) Starting at the end of the second decade New Yorker coronary arteries accumulate increasing amounts of cholesterol, in contrast to the findings in age-matched East Africans. 2. (2) The kinds of lipids (including fatty acids) in the coronary arteries of New Yorkers and East Africans were in general similar. This suggests that (as far as lipids are concerned), the type of arteriosclerosis is the same in both groups; the same conclusion is suggested by light microscopy observations. 3. (3) The selective accumulation of certain cholesterol esters and not of other lipids in the coronary artery suggests that the process is a dynamic one, and does not depend on simple filtration from the blood.

Electron microscopy study of chyle from rats fed butter or corn oil

Abstract In both man and experimental animals butter and corn oil appear to have different biologic effects. We hoped that an electron and phase microscopy study of the mechanics of lipid adsorption following meals of butter or corn oil might provide insight into the biologic action of these two fats. Jejunal mucosa and chyle from the visceral lymphatics of butter and corn oil-fed rats were examined in osmium tetroxide fixed sections embedded in Epon, and chyle was examined directly by phase microscopy. The appearance of lipid in the jejunal mucosa confirmed a previous report that jejunal fat was different in appearance in butter and corn oil-fed rats. In addition, the appearance of fat in the chyle was strikingly different depending on the type of fat fed. In the butter-fed rats the fat, presumably in the form of chylomicrons, appeared either as minute forms with irregular borders, or as large globular masses measuring from 5 to 20 microns in diameter. The lipid in the visceral lymphatics of corn oil-fed rats appeared for the most part as round, smooth bordered spheres up to one micron in diameter with densely staining edges. Rats fed water showed virtually no osmophilic masses which could be interpreted as fat. The meaning of these differing physical appearances of lipid with regard to their biologic effect is not clear. It is possible, however, that the different physical characteristics of chylomicrons from butter and corn oil in the rat may in part account for the different biologic actions of the two fats.

Studies of fibrinogen synthesis in rats fed thrombogenic diets.

Abstract In rats fed complex high fat-cholesterol diets serum lipids and various coagulation factors, including plasma fibrinogen, prothrombin, factors V and VIII, and fibrin-stabilizing factor, were elevated as compared to stock-fed rats. The exact mechanism accounting for the increase in these factors is not clear. In the current experiments we have selected fibrinogen from among the coagulation factors for study of possible mechanism leading to its elevation. Plasma fibrinogen levels in the high fat-cholesterol group increased two- to three-fold, while C 14 -glycine incorporation into fibrinogen in vivo was reduced to less than 10% of control values. These changes began to take place as early as two days after dietary feeding is started. Amino acid incorporation under these circumstances is not necessarily a measure of protein synthesis but does provide us with at least a comparative rate of synthesis. Our data suggest that very likely the elevated plasma fibrinogen level is due to a decreased rate of degradation rather than to increased synthesis. In a cell-free system including microsomes and “supernatant” from liver, oxidative substrate and cofactors required for oxidative phosphorylation and ATP generation, C 14 -leucine incorporation into microsomal protein and response of C 14 -phenylalanine incorporation to poly U were markedly reduced in the high fat-cholesterol fed rats as compared to stock-fed rats. The difference in radioactive amino acid incorporation into polysomal protein between the two groups however was slight, and the response of C 14 -phenylalanine incorporation to poly U was approximately the same in the two groups. Major differences in the ultrastructure of the liver between the two groups were the appearance of rough-surfaced endoplasmic reticulum, characteristic arrangement of ribosomes and presence of lipid in the cytoplasm. In the high fat-cholesterol group endoplasmic reticulum usually appeared disorganized and cisternae irregularly distended. Characteristic rosette or spiral patterns were much less common than in a stock-fed rat and numerous lipid droplets were usually seen. Chemical determinations of RNA content suggest that there is actual decrease in the number of ribosomes in the liver of high fat-cholesterol fed rats. This decrease and the disturbances in arrangement of ribosomes observed by electron microscopy may contribute to the biochemical defects that were demonstrated. However, demonstration of association by itself is not sufficient to warrant more specific conclusions.

Biochemical study of lipids in chyle, blood, and liver of corn oil- and butter-fed rats with phase and electron microscopy correlation

Abstract In both whole chyle and serum of corn oil- and butter-fed rats, the fatty acid patterns resembled that of the lipid fed. In vitro studies have suggested that osmium tetroxide combines with polar end groups of lipids or double bonds of fatty acids. In the corn oil-fed rats, the lipid masses in chyle and within blood vessels had a similar appearance in fresh phase microscopy preparations and in osmium tetroxide-fixed material seen by electron microscopy. In the butter-fed rats, however, lipid in chyle and serum was either artifactually distorted or was not stained at all by osmium tetroxide. In the livers of the water-, corn oil-, and butter-fed rats, a relatively large number of double bonds were demonstrated by lipid analysis in all three groups. In keeping with this finding, osmium tetroxide stainable lipid of similar appearance was found in electron microscopy preparations of the livers from all three groups of rats. The lack of double bonds in the lipid of chyle and serum of the butter-fed rats compared to the corn oil-fed rats possibly explains the behavior of these lipids when fixed with osmium tetroxide. As in a previous study, giant chylomicra were seen both by phase and electron microscopy in the chyle of butter-fed rats. It was not possible, however, to determine whether these chylomicra were not, at least in part, artifactual. No lipid masses were found passing through the vessel walls of either the corn oil- or butter-fed rats, but in this study the maximum resolving power of the electron microscope was not used, and it is possible that further studies may demonstrate lipid masses of specific chemical composition within arterial walls.