Journal of atherosclerosis research最新文献

In previous papers the present author had put forward the hypothesis that elastolytic enzymes play a role in the formation of fibrous plaques (atherosclerotic lesions of grade 2). In order to get more information about the relationship between the concentrations of pancreatic elastoproteinase and elastomucases and the degree of atherosclerosis and senile lung emphysema, more data of necropsied individuals over 50 years of age were collected.

The data clearly demonstrate a high correlation between increased levels of elastolytic enzymes in the pancreas and those stages of atherogenesis and lung emphysema in which metabolic changes in the connective tissue components take place. Since the process of elevated enzyme production in the pancreas seems to precede the formation of severe atherosclerotic lesions, no correlation was found between pancreatic enzyme levels and the severity or complications of atherosclerosis.

The age relationship of pancreatic enzyme production and the influence of elastolytic enzymes on the occurrence of myocardial infarction, as suggested by some authors, still remains unclear.

The extent and severity of arteriosclerosis in rabbit aorta induced by exposure to short periods of systemic hypoxia for two weeks were studied during the hair-shedding period (September through December). Two series of experiments were carried out in relation to two different shedding periods with an interval of 1 year. The entire study involved 152 rabbits. Three experiments were performed in shedding and three in nonshedding periods. While shedding, the rabbits exposed to hypoxia developed slight gross arteriosclerosis in contrast to the severe arteriosclerosis that developed while the animals were not shedding. Qualitatively, the gross and microscopic changes did not differ during and outside the shedding periods. Comparison of the biochemical changes in the aortic acid mucopolysaccharides and collagen induced by the systemic hypoxia during the shedding and nonshedding periods showed no statistically significant differences. The resistance to arteriosclerosis during shedding may be due to hormonal factors, which also may be of importance to the development of arteriosclerosis in other species. Furthermore, the phenomenon has to be taken into consideration in experimental studies of rabbit arteriosclerosis.

Colchicine is known to inhibit clot retraction. We have found that it also inhibits platelet aggregation produced by ADP, by nor-adrenaline and by “collagen”, and that it reduces platelet adhesiveness. The inhibition of aggregation by colchicine does not seem to be mediated by —SH blockade, nor does it depend on the availability of an acetyl side-chain.

Quantitative histochemical estimation of multiple layers of 6 human coronary arteries shows that the triglycerides in coronary atherosclerosis are mainly derived from contaminating adventitial adipose tissue. Only between 4.6 and 24.1 % of the neutral lipids in atherosclerotic intima are triglycerides; sterols and their esters constitute the remainder.

Evidence is presented for an immunological disorder in atherogenesis. At present milk protein is the only antigen known to be involved but there may be others. This disorder offers a means of integrating many existing facts about atherosclerosis that are otherwise apparently unrelated. The hypothesis embraces both the filtration concept and also the thrombogenic theory.

Female breeder rats develop spontaneous arteriosclerosis if they are actively and repeatedly bred. Females which nursed large litters following each pregnancy appeared to develop the most severe arterial disease as well as other degenerative changes. In order to determine how the degree of lactational activity would affect the pathogenesis of the arterial disease female breeder rats were provided with many, few or no pups during the lactation phase following each of 4 pregnancies. To test the effect of abrupt cessation of milk removal vs. complete removal of milk, breeder females were provided with many pups to nurse following each of 4 pregnancies. However, in some cases the young were removed suddenly, i.e., forced weaning, after 23 days of lactation, whereas some females were permitted to nurse their young until they gave up nursing voluntarily, i.e., natural weaning. A special group of breeders completed 1 pregnancy only but was provided with nursing pups for an extended period of time, i.e., 100 days.

The results of these experiments demonstrated, that female breeders which had experienced one or several pregnancies and which had lactated actively followed by abrupt weaning of the young developed grossly visible arteriosclerosis characterized by severe calcific complications. On the other hand, breeders which were permitted to suckle their young until they were weaned naturally were completely free of the severe calcific arterial involvement. However, early microscopic intimal mucopolysaccharide accumulations capped by collagen could be found in all breeders. These intimal lesions are believed to be the forerunners of the more complicated lesions and are believed to be associated with the gestational phase of the reproductive cycle.

The incorporation into lipids of [¹⁴C]glucose and [¹⁴C]palmitate with and without unlabelled glucose in defined samples of apparently normal, fresh human intima and media was measured in vitro. After incubation of the intima samples with [¹⁴C]-glucose about 50 % and 15 % of the label occurred in triglycerides and lecithin, respectively. A moderate degree of activity was found in phosphatidyl inositol and cholesterol and/or diglyceride; in other lipid classes the activity was low with the exception of a varying degree of label in free fatty acids. After incubation with [¹⁴C]palmitate the distribution of label was similar but the proportion of label in triglycerides and lecithin was reversed and the degree of labelling of sphingomyelin was higher. After addition of unlabelled glucose the above differences for the [¹⁴C]-glucose and [¹⁴C]palmitate precursors were partially levelled out. The differences were less pronounced for the media samples. The rates of incorporation of the respective precursors were similar in intima and media both on a dry weight and DNA basis.

The distribution of label in triglycerides and lecithin after incubation with [¹⁴C]palmitate agrees well with results obtained by others for species susceptible to experimentally induced or spontaneous atherosclerosis but deviates from more atherosclerosis-resistant species. It is possible that this correlation reflects important factors for the formation of atherosclerosis.

[4-¹⁴C]Cholesterol was injected intravenously in rats fed on cholesterol-enriched lactose, sucrose and stock diets. It was metabolized and excreted into the bile faster in the control cholesterol-fed group than in the two sugar-supplemented groups; in the sucrose group faster than in the lactose group. In the control group, the specific activity of cholesterol was high in the small intestine soon after oral administration of [4-¹⁴C] cholesterol, but it remained low in the plasma and liver. Conversely, it was low in the small intestine but high in the plasma and liver in the lactose group. Although the uptake of cholesterol was much greater in the intestinal wall in the control group, it did not appear to be transported easily into the plasma: the converse applied in the lactose group.

The marked hypercholesteraemia induced by the lactose-cholesterol diet might be due to decreased cholesterol metabolism and increased cholesterol absorption and transport from the intestine.

Serial estimation of plasma fibrinogen in patients with acute myocardial infarction showed a rise after admission, reaching a peak level on the 5th day. No correlation was noted between this response and the age of the patient, SGOT level, serum cholesterol value and clinical course while in hospital.

Oxidation of [1-¹⁴C] acetate to ¹⁴CO₂ and its incorporation into liver cholesterol in guinea pigs was not significantly altered in case of chronic hypovitaminosis C. Conspicuous accumulation of total cholesterol in the liver of guinea pigs with chronic hypovitaminosis C cannot be explained in terms of a change in acetate metabolism.