Journal of atherosclerosis research最新文献

Platelet adhesiveness, degree of atherosclerosis and plasma cholesterol content were examined in rabbits fed for 62 weeks a diet deficient in essential fatty acids (EFA) containing 40 cal % hardened coconut oil, or diets in which 10 cal % of the hardened coconut oil had been replaced by linseed oil (rich in linolenic acid) or by safflower oil (rich in linoleic acid).

Additionally, histopathological and clinical investigations, were carried out to gain some information about the consequences of feeding rabbits a diet deficient in EFA for a prolonged period. The results are:

• (1)

  The three dietary groups showed no significant differences as to platelet adhesiveness to glass.

• (2)

  Atherosclerosis of the aorta was more severe in the hardened coconut oil group (Mean Atheroma Index = 2.33) than in the linseed oil group (m.a.i. = 1.00) or the safflower oil group (m.a.i. = 0.25). The frequency of coronary artery changes was also significantly higher in the hardened coconut oil group than in the two other groups. One animal of the hardened coconut oil group showed a myocardial infarction.

• (3)

  The plasma cholesterol content was significantly higher in the hardened coconut oil group than in the two other groups.

• (4)

  All but one animal of the hardened coconut oil group showed a cirrhotic liver, whereas the animals of the other two groups displayed hardly any liver changes.

• (5)

  Haemolysis time in isotonic thiourea solutions showed significant differences between all dietary groups of rabbits. The hardened coconut oil group showed the shortest time; the safflower oil group the longest.

A positive correlation was found between haemolysis time and the polyunsaturated fatty acids content of the erythrocytes. Since their saturated fatty acid content was fairly constant, a negative correlation also existed between the haemolysis time and the monounsaturated fatty acid content. However, this correlation was not found within every dietary group since either the number of individual values is insufficient or the correlation is spurious.

The conclusion is drawn that linseed oil has no specially favourable effect on platelet adhesiveness or atherosclerosis. With regard to the latter aspect, safflower oil is preferable.

Attention is drawn to a previous study by the authors in which the severity and extent of cerebral atherosclerosis in the Japanese and Minnesota populations were reported. This study indicated a possible ethnic difference in severity of atherosclerosis in the arterial circle of Willis between the Japanese and Minnesota populations in the direction of greater involvement in the Japanese. 375 Japanese autopsies were added to the series since that report.

The present study shows that there is a difference in the pattern of vessel involvement between the two groups. In the Minnesota cases first lesions are found primarily in the large caliber vessels of the circle of Willis, whereas in the Japanese cases some small caliber vessels show frequencies of single plaques almost equal to those in the large vessels. Moreover, a comparison of the degree of atherosclerosis in individual vessels indicates that it is in the smaller vessels that the Japanese cases present more severe involvement than the Minnesota cases.

Among our female breeder rats, there is a high incidence of post-reproduction arteriopathy due to forced weaning of their offspring. In the chronic stage, these vascular lesions are very similar to the so-called spontaneous arteriosclerosis of breeder rats which has been described previously by other authors.

The present report deals with the influence of 3 different standardized diets on the development of this arteriopathy in rats. The vascular lesions were found to occur after only 1 of these 3 diets. On the other hand, biochemical changes in the blood calcium and/or phosphorus levels were observed (after forced weaning) with all the diets investigated.

These results do not support our previous hypothesis concerning the basic importance of changes in the level of blood phosphorus in the pathogenesis of post-reproduction arteriopathy (beginning as pure mediocalcinosis), even though fluctuations in the blood calcium and phosphorus levels after forced weaning should be studied further in this context.

A technique of in situ perfusion of rabbit abdominal aorta permitted measurement of rates of aortic lipid synthesis in conditions approaching the physiological. Aortic synthesis of fatty acids proceeded by both chain elongation and de novo pathways. Fatty acids synthesised in aorta from glucose were a quantitatively unimportant source of aortic lipid whereas perfusate free fatty acids were rapidly incorporated into aortic ester lipid. Aortic lipid glycerol was synthesised from labelled glucose and more than 96 % of the label in aortic lipid was in non-fatty acid moieties. While tri- and diglycerides were synthesised in aorta from perfusate glucose and free fatty acids, aortic phospholipids were the major ester-product (> 56 %) of these substrates. Phosphatidylcholine was the major phospholipid synthesised and was formed by de novo synthesis although data was also compatible with the presence of a lysophosphatide pathway in intima. Phosphatidylinositol was rapidly synthesised and glucose carbon entered glycerol but not inositol of this lipid.

The possibility of contamination of aortic lipid with radioactive lipid from periaortic adipose tissue was emphasised by the demonstration that rates of lipid synthesis from various substrates were 30–400 times greater in periaortic adipose tissue than in aorta.

Experimental arteriosclerosis was induced in the aorta of male albino rabbits by daily exposure to short periods of systemic hypoxia through 2 weeks.

An increase of the inner surface area of aorta and gross arteriosclerotic changes in 13 out of 16 rabbits reflected an injury to the aortic wall produced by systemic hypoxia. The aortic content of acid mucopolysaccharides, the synthesis of sulpho-mucopolysaccharides, and the mucopolysaccharide to collagen ratio were increased. Regression analysis showed an increase of the mucopolysaccharides and collagen parallel to the increase of the inner surface area. This correlation supports the interpretation of the biochemical alterations as non-specific processes of repair elicited by a damage to the aortic wall.

• 1.

  Arterial hypertension induces changes in the mesenchymal metabolism of rat aortic wall. This can be demonstrated by high increases of [³⁵S]sulfate incorporation into aortic sulfomucopolysaccharides.

• 2.

  Arterial hypertension is also accompanied by changes in lipid concentration of the vessel wall. This was shown for cholesterol, palmitic, oleic and linoleic acid, which all show definite increases in concentration.

• 3.

  The increase of lipid concentration in the vessel wall is almost entirely due to lipid material penetrating the wall from the blood stream, however it cannot be decided whether this is due to increased inflow or decreased outflow of lipids in the vessel wall.

• 4.

  Increased lipid concentration in the vessel wall is not an immediate consequence of arterial hypertension, since it begins developing after intensive changes in the mesenchymal metabolism and in experiments with acute hypertension of short duration even hours after blood pressure has returned to normal values.

• 1.

  Durch Hochdruckeinwirkung ensteht in der Aortenwand von Ratten regelmäßig eine Mesenchymstoffwechselstörung, nachweisbar am erheblich erhöhten [³⁵]S Sulfateinbau in Sulfomukopolysaccharide.

• 2.

  Arterieller Hochdruck bewirkt ebenfalls eine Veränderung der Lipidkonzentration in der Gefäßwand, und zwar im Sinne einer Zunahme der Cholesterin- und Fettsäurenkonzentration.

• 3.

  Die Einstrom-Abstrom-Differenz der Lipide in der Aortenwand ändert sich ebenfalls nach Hochdruckeinwirkung, sie ist die Ursache für die unter 2. genannten Veränderungen.

• 4.

  Die Veränderungen im Lipidgehalt der Gefäßwand sind nicht unmittelbare Folge des Hochdrucks, sondern sie entstehen sekundär durch die hochdruckbewirkte Mesenchymstoffwechselstörung in der Gefäßwand, die eine Transitstörung bewirkt.

A new intravenous fat tolerance test was performed in a group of younger and a group of older male normolipidemic subjects, as well as in a group of male patients with hyperlipoproteinaemia. In this tolerance test the disappearance of an injected fat emulsion from blood was characterized by 2 rate constants: K₁ that describes the maximal removal rate and K₂ that measures the fractional removal rate of the injected triglycerides.

K₁ did not vary with age or correlate with either K₂ or the plasma triglyceride level. K₂ was lower in the older than in the younger control subjects. The older subjects also had higher plasma triglyceride values. K₂ was furthermore significantly lower in the hyperlipidaemic patients than in the old control subjects; all the former patients had K₂-values below the mean value for the older control group.

When all values for K₂ and plasma triglycerides were plotted against each other, K2 was found to decrease with increasing concentration of triglycerides in a hyperbolic fashion. The clinical use of the intravenous fat tolerance test, the possible physiological basis of K₁ and K₂, as well as the clinical implications of reduced fat tolerance were briefly discussed.

The macromolecular structural stability of lesion-free specimens of human aorta was analysed histochemically. In contrast to those sites less susceptible to atherosclerosis (interbranch zones, arch and anterior wall of the thoracic segment), the aortic regions most severely involved by this disease (branch orifices, abdominal portion, posterior wall of the thoracic segment), showed the following characteristics: (i) more rapid and intense dissolution of intimai ground substance mucoproteins following histochemical methods that rupture some non-covalent and covalent linkages; (ii) greater sensitivity to electrostatic-bond-breaking reagents, as shown by the solubility of a hexose-protein fraction which may be the main argyrophilic component of intimai reticulin fibres; (ii) increased solubility (especially with hydrogen-bond-breaking solutions) of the fuchsinophilic material of intimai collagen fibres.

Evidence is presented for the existence of β-adrenergic receptors effecting disaggregation of clumped platelets. This function is mediated by adenosine 3′-5′ cyclic monophosphate.