A.S. Daoud

Inhibition of atherosclerosis by cod-liver oil in a hyperlipidemic swine model

We studied the effect of cod-liver oil on the development and progression of coronary artery disease in swine subjected to coronary balloon abrasion and fed an atherogenic diet for eight months. Sections from serial 3-mm segments of the coronary arteries were analyzed morphometrically in 7 pigs given a cod-liver-oil supplement and 11 control animals not given the supplement. Significantly less disease was seen in the sections from the animals fed cod-liver oil. The mean lesion area per vessel, mean luminal encroachment per vessel, and mean maximal luminal encroachment per vessel were reduced in animals fed cod-liver oil, as compared with controls, (P = 0.05, P = 0.016, and P = 0.011, respectively). Both groups of animals had severe hyperlipidemia throughout the study. Differences in the extent of coronary atherosclerosis were not related to differences in plasma lipid levels. Platelet arachidonate was markedly reduced, platelet eicosapentaenoic acid was increased, and serum thromboxane was decreased in the oil-fed group as compared with the control group. We conclude that in our animal mode, dietary cod-liver oil retarded the development of coronary artery disease, possibly through changes in prostaglandin metabolism.

Aneurysms of the coronary artery

Abstract Ten cases of arteriosclerotic aneurysms of the coronary arteries have been reported. In addition, all cases of coronary artery aneurysm in patients over the age of 16 years have been compiled and tabulated. Certain statistical conclusions have been drawn. Arteriosclerotic coronary arterial aneurysms were found in association with abdominal aortic aneurysms in 8 of 10 cases. This association has been noted previously. Pathogenesis has been briefly considered. The cases we have reported represent the result of a meticulous technic of dissection of the coronary circulation. Aneurysms of the coronary artery are probably not as rare as the previously low number of case reports might have indicated and represented 1.4 per cent of the autopsies at Albany Medical Center Hospital during the period of study.

Aortic media explants cell proliferation and production of mucopolysaccharides, collagen, and elastic tissue☆

Abstract Segments of pig aortic medial tissue, cultured in a semisynthetic medium, develop a new growth starting about the fourth day. In the first week most cells in this new growth are primitive cells and fibroblast-like cells with only a few modified smooth muscle cells. At this period, only mucopolysaccharides can be identified in the extracellular substances. By the third week, the great majority of cells are modified smooth muscle cells. The extracellular substance is composed of collagen and elastic tissue in addition to mucopolysaccharides. Since the two phenomena, cell proliferation and the production of these specific extracellular substances, are among the most prominent features of early atherosclerosis, it would seem that this in vitro system could be used advantageously in experiments designed to study the role of individual factors implicated in atherogenesis.

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.

Association of DNA synthesis and apparent dedifferentiation of aortic smooth muscle cells in vitro

Abstract Smooth muscle cells (SMC) of medial explants of swine thoracic aortas appear to undergo in the first few days of culture rapid dedifferentiation toward more primitive forms. The number of cells synthesizing DNA in the explants increases as the number of well differentiated SMC decreases. Electron microscopic autoradiography revealed that more of the cells incorporating 3 H-thymidine were poorly differentiated SMC. Thus it appears that in this in vitro situation dedifferentiation of SMC precedes rapid cell proliferation. In early cholesterol-induced atherosclerosis in swine many partially or completely undifferentiated cells are present. The results of the current in vitro study suggest that the undifferentiated cells in the atherosclerotic lesions could arise from mature SMC through dedifferentiation.

Regression of Advanced Atherosclerosis in Swine

Advanced complicated atherosclerosis was produced in the abdominal aorta of swine by a combination of mechanical injury and high-cholesterol, high-fat diet for four months. After removal of the high-cholesterol diet and placing the animal on swine mash for 14 months, there was a significant (P less than .005) decrease in size of lesions with remodeling of the intima toward a smooth surface. Sudanophilia had virtually disappeared and atheromas were almost absent in the regression group, as were thrombosis and hemorrhage in plaques. Cell proliferation, as judged by the number of labeled cells in autoradiography, was less pronounced in this group. There was no decrease in the numbers of segments showing calcification; however, the size of the calcified areas was smaller in the regression group than in the base line. The data suggest that advanced atherosclerosis is susceptible to regression on removal of the atherosclerotic stimulus.

“Preatheroma” phase of coronary atherosclerosis in man

Abstract “Preatheroma” is a term which we apply to the proliferative changes in the arterial wall which develop prior to the occurrence of atheroma. The changes are characterized chiefly by smooth muscle cell proliferation with extracellular fibrillar and nonfibrillar material. The preatheromatous lesion is similar to the atheroma in that it is a focal intimal lesion in the sense that some areas of the intima are involved to a greater degree than others. Preatheroma is more extensive in populations known to develop extensive atheromatous changes, such as North Americans, in contrast to certain Africans in whom atherosclerosis is seldom severe even in old age. Finally, atheroma is always preceded by an appreciable degree of preatheromatous changes. In our opinion, preatheroma is an integral part of the atherosclerotic process and a precursor of atheroma.

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.

Comparison of pathologic and angiographic findings in a porcine preparation of coronary atherosclerosis.

Coronary atherosclerosis was induced in Yorkshire swine by diet-induced hyperlipidemia and balloon intimal abrasion of a coronary artery. Severe stenoses pathologically similar to the lesions of human atherosclerosis were seen after 8 months of the atherogenic regimen. To examine the relationship between the angiogram and pathology in the assessment of the extent and location of coronary atherosclerosis, antemortem angiographic results were compared with results of pathologic examination. Vernier caliper measurements of the coronary angiogram were compared with results of morphometric evaluation of perfusion-fixed coronary arteries. Isolated focal stenoses were correctly localized and quantified, as were focal lesions within vessels diffusely diseased. Both overestimation and underestimation of lesions occurred at bifurcation sites. Diffuse disease without focal stenoses was not well demonstrated angiographically. Vessels that were angiographically thought to be normal or only minimally diseased demonstrated significantly larger lumens angiographically than pathologically. This is believed to be due to fixation and paraffin-processing artifact, even though fixation was performed by perfusion at physiologic pressure. The demonstration of an excellent correlation between the luminal size as determined angiographically and morphometrically at sites of focal obstruction confirms the value of quantitation of coronary angiograms in vivo as a diagnostic tool in coronary atherosclerosis.

Increased DNA synthesis in aortic explants from swine fed a high-cholesterol diet☆

Abstract Medical explants from the thoracic aorta of swine fed a high-cholesterol (HC) diet, when cultured 4 or 9 days in semisynthetic medium containing serum at 20, 40, 60, or 80% concentration, show a higher rate of DNA synthesis, as measured by incorporation of 3 H-thymidine into DNA, than their paired controls from swine on a normal diet. This increased rate of DNA synthesis was independent of whether the serum supplement was normal or HC. Thus it appears that the HC diet has produced some changes in the medical cells which enhanced the growth potential of these cells. In general, HC serum in the medium resulted in a higher rate of DNA synthesis than normal serum in explants from swine on either a conventional or an HC diet.