Formation Of Atheromatous Lesions Research Articles

In vivo effects of cis-5,8,11,14,17-20:5 (n-3) and cis-4,7,10,13,16,19-22:6(n-3) on serum lipoproteins, platelet aggregation, and lipid metabolism in the aorta of rats.

Highly purified cis-5,8,11,14,17-20:5 (n-3) or cis-4,7,10,13,16,19-22:6 (n-3) was administered to rats for 2 weeks, and serum lipoprotein lipid levels, platelet aggregation, and lipid metabolism in the aorta in vivo were investigated. 20:5 (n-3) decreased the level of low density lipoprotein phospholipid. 22:6 (n-3) increased the level of high density lipoprotein cholesterol and decreased those of low density lipoprotein triglyceride and phospholipid. Both 20:5 (n-3) and 22:6 (n-3) markedly inhibited platelet aggregation. 20:5 (n-3) decreased the acid and neutral cholesterol esterase activities, but did not affect either acyl-CoA synthetase or acyl-CoA: cholesterol acyltransferase activity. 22:6 (n-3) had no effect on any of these enzyme activities. From these results, the roles of 20:5 (n-3) and 22:6 (n-3) in the formation of atheromatous lesions and the mechanism of the decrease in cholesterol esterase activity by 20:5 (n-3) were discussed.

Focal alterations in metabolic capabilities associated with development of cholesterol-induced atheromatous lesions: A quantitative cytochemical study

Succinic dehydrogenase (SDH), glucose-6-phosphate dehydrogenase (G-6-PDH), and lactic dehydrogenase (LDH) activities were measured in thoracic aorta sections obtained from hypercholesterolemic New Zealand White rabbits in order to characterize metabolic alterations associated with early atheromatous lesion development. Quantitative cytochemical and micrometric techniques were employed to assess enzyme activities within various zones of the vessel wall (intima, inner-, mid-, and outer-tunica media) during lesion development. In aortic sections from control (normocholesterolemic) rabbits, and in nonlesion segments from hypercholesterolemic rabbits, oxidative enzyme activity was uniform and constant among the three zones of the tunica media; activity in uninvolved (nonlesioned) aortic segments excised from cholesterol-fed rabbits did not differ from control levels. In regions of mural lipidosis, however, the intima exhibited markedly elevated activities of SDH, G-6-PDH, and LDH in comparison to the normal rabbit media. From the onset of lesion formation, metabolic alterations (increased G-6-PDH and LDH activities) were evidenced in smooth muscle cells of the inner media. With progressive intimal thickening, increased enzymatic activity was also observed in outer zones of the tunica media. Transmural medial gradients in enzymatic activity were noted in severely lesioned sites. G-6-PDH and LDH activities were greatest in the inner media; SDH activity, however, was greatest in the outer media. The overall data indicate that atheromatous lesion formation is associated with elevated metabolic capabilities within the intima and entire smooth muscle cell population which underlies aortic lesion sites, and that the observed cellular transformations occur only after the onset of mural lipidosis.

脂肪酸代謝の研究 (4)

We investigated the characteristics of fatty acid metabolism in rat aorta and brain microvessels. Brain microvessels were prepared by the modification of the method by Brendel et al. It was confirmed that brain parenchymal tissues were not microscopically and immunologically contaminated.[1-14C] palmilate was much more incorporated into brain microvessels than into aorta, and it was mainly incorporated into esterified lipid in aorta and into cot in brain microvessels. In high cholesterol diet-fed rat aorta, [1-14C] palmitate, oleaste, linoleate and octanate were more incorporated into cholesterol ester compaired with controls while in brain microvessels they were not. Both enzyme activities of acyl-coA synthetase and acyl-coA: cholesterol acyltransferase increased in high cholesterol diet-fed rat aorta, however, such changes could not be seen in brain microvessels. These data show one of the mechanisms of formation of atheromatous lesions which are easily formed in aorta and rerely formed in brain microvessels. On the other hand fatty acid oxidation activities were much higher in brain microvessels than in aorta or heart or liver. Fatty acid oxidation activities in brain microvessels of spontaneously hypertensive rats (SHR) decreased compared with normotensive rats whereas the decrease was not found in aorta or heart. Fatty acid oxidation activies in brain microvessels of SHR decreased at the age of 16-29 weeks at which hypertension persisted, but they did not change at the age of 9 or 14 weeks at which hypertension was not completed. These results suggest that persistent hypertension may cause decreased activities of fatty acid oxidation in brain microvessels. Both activities of acyl-CoA synthetase and carnitine acyltransferase did not decrease in brain microvessels of SHR, suggesting that intramitochondrial oxidation activities might be decreased.

Chronic lathyrism and atheromatosis in the rat. Protective effect of metformin.

Chronic administration of beta-aminopropionitrile fumarate (BAPN) (1 g/kg/day for 9 weeks) produced morphological changes of the aorta wall and in dermis, and biochemical changes of the aortic wall in the rat. Chronic administration of BAPN did not produce plasma lipid abnormalities such as those due to hyperlipidic diet. 9 weeks of BAPN followed by 10 months of a hyperlipidic diet increased the aortic cholesterol level and induced atheroma. The diet alone only produced an endothelial lipid overload and increased the aortic cholesterol level but less than BAPN and hyperlipidic diet together. Addition of metformin to BAPN prevented the formation of atheromatous lesions in the aorta and minimized the level of lipids in the aortic wall and of the dermis.

The effect of elastoproteinase on experimental atheromatosis in rabbits

The effect of elastoproteinase treatment of rabbits fed for 12 weeks with a hypercholesterolemic diet was studied in two series of experiments: the therapeutic effect of the enzyme after the 12-week period and the prophylactic effect during the 12-week period. The concentration of cholesterol and lipid-phosphorus in the whole blood and in the α- and β-lipoprotein fractions was affected in such a way that nearly all the concentrations were significantly higher in the combined enzyme-cholesterol treated rabbits than in the cholesterol animals. Further, enzyme treatment (even of the control animals) drastically decreased the elastin content in lung, heart and aorta, while at the same time the content of soluble collagen was largely increased. The conclusion may be drawn that elastoproteinase cannot be used to prevent or affect positively hypercholesterolemia and the formation of atheromatous lesions.

The influence of trauma on experimental aortic atheromatosis

Summary The influence of blunt aortic trauma on the development of experimental atheromatosis has been observed in rabbits fed normal as well as high cholesterol diets. Trauma alone did not produce a significant degree of atheromatous change within the 65 day period of these experiments. Trauma did not accelerate the formation of atheromatous lesions at the site of injury. The earlier appearance of generalized abdominal aortic atheromatous lesions in the traumatized animals fed a high cholesterol diet is unexplained.