Modification of two types of cholesterol atherosclerosis in rabbits by blocking lipoprotein lysine epsilon-amino groups.

In previous studies, it was shown that a lysine deficient diet reduces the severity of aortic cholesterol atherosclerosis in rabbits. Feeding 1-amino-3-imino N,N' propene diacetate (AIPD) produced 2 metabolic by products with active aldehyde groups 1-amino propenal acetic acid (APA) and malonyldialdehyde (MDA) that transiently block the lysine epsilon-amino groups of all proteins and lipoproteins in vivo. This paper reports the effects of blocking the lysine free epsilon-amino groups of all lipoproteins on 2 different types of cholesterol atherosclerosis; (1) A proliferative-type cholesterol atherosclerosis containing a high proportion of spindle-shaped myogenic foam cells rich in collagen and alcian blue-stainable material produced by feeding a diet containing cholesterol, peanut oil, ethanol and butylated hydroxyanisole and (2) cholesterol atherosclerosis containing a high proportion of polyhedral-shaped nonmyogenic macrophage-type foam cells produced by feeding cholesterol and oleic acid. After 14 weeks on the diets the mean +/- SD percent of intimal aortic area covered with the myogenic-type atherosclerosis in the control peanut oil-fed group was 34 +/- 6% and this was reduced to 13 +/- 3% in the peanut oil AIPD group. In contrast, after 14 weeks in the control oleic acid group the severity of atherosclerosis was 14 +/- 4% and this was increased to 36 +/- 7% in the oleic acid AIPD group. Aortic cholesterol concentration was decreased in the AIPD peanut oil group relative to its control but was increased in the AIPD oleic acid group relative to its control group. A higher concentration of AIPD metabolites accumulated in the atherosclerotic lesions of the oleic AIPD group than in the peanut oil AIPD group indicating that a larger amount of lysine blocked lipoprotein accumulated in the macrophage-rich lesions of the oleic acid AIPD group than in the myogenic-rich lesions of the peanut oil AIPD group. Blocking lysine epsilon-amino groups in vivo by feeding AIPD did not modify DNA synthesis in the aortae of either AIPD group relative to their control groups.

Effects of estradiol on myointimal thickenings from catheter injury and on organizing white mural non-occlusive thrombi.

The objective of this present study was to determine the effect of estradiol on the organization of white, mural, nonocclusive thrombus produced with a permanent, indwelling catheter in the abdominal aortae of rabbits and on myointimal thickenings produced by catheter injury but with only transient adhesion of platelets and no thrombosis in the thoracic aorta. Estradiol did not significantly alter the weight of thrombus or myointimal thickenings produced nor did it qualitatively or quantitatively alter Evans Blue uptake by the 7-day myointimal thickenings from injury or alter Evans Blue uptake by the 7-day thrombus. DNA synthesis measured in terms of [3H]thymidine incorporation into biochemical extractable DNA and expressed as dpm/mg DNA was 9 519 for the normal rabbit aortic wall without adventitia; 358 261 for myointimal thickenings including underlying aortic wall without estradiol treatment and 196 336 with estradiol; 55 840 for thrombus without estradiol and 55 250 with estradiol. Expressed as dpm/mg delipidated tissue the values were 62 for the normal rabbit aortic wall; 4 590 for myointimal thickenings without estradiol and 2 037 with estradiol; 1 421 for thrombus without estradiol and 1 403 with estradiol. Estradiol was effective in reducing DNA synthesis in the myointimal thickenings from injury but was not effective in reducing DNA synthesis in the 7-day thrombi. Estradiol significantly increased the influx or retention of [14C]cholesterol found at autopsy in both the organizing thrombi and the myointimal thickenings from injury after an oral dose of 14C-labelled cholesterol was administered 4 days prior to autopsy; however, estradiol did not significantly modify the final cholesterol concentration in the lesions.

Depth in training in academic pathology including teaching and research.

Excellent training in academic pathology, including research, results when teaching becomes the prime function of the scholars in an academic department. Teaching of postgraduates requires research and practice and furthermore requires excellence in these fields. A program designed to teach the postgraduates orientates the research and practice to this end rather than making these ends in themselves. A major aim of pathology is to explain at the cell level the mechanism of interaction between intrinsic and extrinsic factors resulting in the abnormality of cell function in disease. The traditional core training in tissue diagnosis develops the interest and ability to analyze the cell and its intracellular activities. To realize the relation of structure and function as the ultimate aim of pathology an intensive study of some of the collateral fields of cell chemistry, physiology, immunology and genetics must become a major part of the organized program.

Smooth muscle cell changes of media underlying experimental arterial thrombosis.

The is much evidence that platelet thrombi release many factors which can alter endothelial permeability and may alter other cell membrane permeability. A large thrombus could also interfere with the diffusion of oxygen to the inner media. In either case injury of the medial cells may affect their ability to metabolize lipid.

Lipid profile in the evolution of experimental atherosclerotic plaques from thrombus.

Nonocclusive white mural thrombosis was induced in the abdominal aortae of normolipidemic rabbits by insertion of a polyethylene catheter into the abdominal aortae. The thrombus subsequently organized into intimal thickenings which resembled fibrofatty type atherosclerosis seen in man, showing large numbers of foam cells containing stainable lipid, fatty necrotic centers, cholesterol clefts, calcification, and fibrous caps. The lipid composition of the thrombus and lesions was followed at serial time intervals from 4 hours to 60 weeks. Lipid analysis showed significant concentrations of lipid in the early lesions and with time these lipid concentrations increased and later decreased. These studies demonstrate that the fibrofatty lesions derived from a white thrombus have significant amounts of the same lipids that characterize the atherosclerotic lesions of man, however, there is a lower proportion of cholesterol to the other constituents and a higher proportion of phospholipids. The free cholesterol and cholesteryl ester of the 4-day lesions were much greater than that of platelets alone indicating that significant amounts of plasma are trapped in a thrombus when it forms.