[Regression of atherosclerosis lesions]. / Uber die Regression atherosklerotischer Läsionen.

The regression of even advanced atherosclerotic vascular lesions is now well-documented in various animal species (dogs, pigs, rabbits, birds and monkeys). In man, well-controlled studies in selected groups of patients have already shown that a reduction of luminal stenosis may take place. After a reliable morphological und morphometric validation has been obtained, non-invasive and easily applicable methods are available which allow reproducible documentation of the reduction in lesions.

Influence of CDP-choline administration on the aortic wall lesions in dietically hypercholesterolaemic rabbits: a morphometric evaluation.

In New Zealand rabbits subjected for a 2 month period to a 1% or 2% hypercholesterolic diet, larger intimal involvement and histologically heavier lesions were observed in the animals on a hypercholesterolic diet. The intimal involvement was larger in the aortic arch. In groups of rabbits simultaneously subjected to similar diets and to i.v. CDP-choline injections, the intimal involvement appeared reduced (p less than 0.01) both in the arch and in the descending tract of the thoracic aorta.

Atherosclerosis and aging. A morphometric study on arterial lesions of elderly and very elderly necropsy subjects.

A histomorphometric study was performed on arterial wall lesions of different arterial regions (arch, thoracic, abdominal parts of the aorta; right and left common and internal carotid arteries; coronary arteries; and basilar and middle cerebral arteries), collected from 108 elderly and very elderly (greater than 90 years of age) subjects who underwent necropsy. Lumen stenosis percentage, mean intimal thickening, and mean thickness of the media were measured by means of a computerized system using a manual input and graphic printout; statistical tests were performed using variance and regression analysis. Results showed that the arterial wall lesions in patients over 60 years of age tend to be stabilized in all regions studied except for the cerebral region, where the lesions tend to have a continuous progression related to age, even in a group of subjects over 90 years of age.

Some pathogenetic aspects of atherosclerotic lesions. Platelets and atherogenesis. Differences in atherogenesis in different body districts. Regression of arterial lesions in animal models.

The first part of the paper is devoted to the role of platelets in atherogenesis because the new ultrastructural techniques have revealed the morphological basis of platelet "activation". In the second part, the delayed involvement of intracranial vs extracranial cerebral arteries, afferent to the brain is examined on the basis of recent work both in man and in experimental animal models. Regression of arterial lesions is considered in the third part chiefly on the basis of contributions in experimental animals, while more data on regression in humans are expected in the near future.

Delayed intimal lesion development in cerebral arteries versus aortic and carotid arteries of spontaneously hypertensive rats.

The development of intimal lesions is delayed in spontaneously hypertensive rats (SHR) in cerebral versus aortic and carotid arteries. The reason for this delayed involvement needs further study.

Ultrastructural aspects of cynomolgus atherosclerotic carotid artery lesions on cholestyramine 'regression' treatment.

The carotid artery lesions of atherosclerotic cynomolgus monkeys treated with cholestyramine and studied with scanning electron microscopy appeared to be less bulging and largely covered by endothelial cells. With transmission electron microscopy these lesions showed an evident disappearance of cells and of extra- and intracellular lipid; a marked relative increase of fibrous material in the intercellular matrix, chiefly collagen and elastin fibers, was noted.

Delayed development of intimal lesions in cerebral arteries of spontaneously hypertensive rats subjected to a short-term atherogenic diet (TEM observations).

In adult spontaneously hypertensive rats, subjected to an atherogenic diet (2% cholic acid in a 5% hypercholesterolic diet) for 19 weeks both aortic and carotid artery lesions were already detectable on TEM examination while the cerebral arteries did not show any lesions. Similar findings have been previously obtained in rabbits and in monkeys on atherogenic diets.

Increased plasma and aortic triglycerides in rabbits after acute administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Administration of a single nonlethal dose (20 micrograms/kg) of 2,3,7,8-tetrachlorodibenzo-p-dioxin to New Zealand male rabbits, both on a standard and on a cholesterol (0.5% in the diet) regimen, resulted in a significant increase of plasma triglyceride levels. Triglycerides were particularly raised in the very low-density lipoprotein fraction; no significant apolipoprotein changes, as assessed by an analytical isoelectrofocusing procedure, could be determined. Concomitant to the increased triglyceridemia, aortic triglycerides were also significantly elevated in 2,3,7,8-tetrachlorodibenzo-p-dioxin-pretreated rabbits, both on the standard and on the cholesterolemic regimen. These findings suggest that 2,3,7,8-tetrachlorodibenzo-p-dioxin, possibly by inhibiting triglyceride breakdown, may induce an atherogenic form of hypertriglyceridemia in a standard experimental model of atherosclerosis.

[Preliminary observations on the structure of the medio-intimal area of the rabbit coronary arteries. (A. Observations on 4-month-old rabbits)]. / Osservazioni preliminari sulla struttura dell'area di giunzione medio-intimale nelle coronarie di coniglio. (A. Osservazioni in conigli a 4 mesi dalla nascita).

The presence of the diffuse intimal thickening (DIT) is commonly considered the structural basis for the early atherosclerotic involvement of the coronary arteries. In the ambit of a systematic morphometric comparison of experimental atherosclerotic plaques of aorta and coronaries, we have studied the coronary medio-intimal junctions of 4 months old rabbits. Both at sub-epicardic and intra-myocardic coronary arteries level we have found fiber structures similar to DIT. These findings may help explaining why coronary atherosclerosis in rabbits does not represent, in the usual experimental models, a lesion particularly severe nor of precocious appearance.

[Preliminary observations, at the ultrastructural level, on the reactivity of cerebral arteries from New Zealand rabbits to combined atherogenic stimuli (hypercholesterol diet and hypertension)]. / Osservazioni preliminari, a livello ultrastrutturale, sulla reattivita' delle arterie cerebrali di coniglio New Zealand a stimoli aterogeni combinati (dieta ipercolesterolica e ipertensione).

Both in monkeys (Rhesus and Cynomolgus) and in New Zealand rabbits fed an atherogenic diet, a marked delay in the appearance of atherosclerotic lesions of the cerebral arteries in comparison with other arterial districts has been observed. This appearance has been described in monkeys as relatively earlier if hypertension is added to the atherogenic diet. Preliminary observations on a little group of rabbits on a 3 months hypercholesterolic diet, subjected to Goldblatt aortic coarctation, have shown an increase of blood pressure and a severe gross atherosclerotic involvement of aorta, resembling the one obtainable after 6 months of atherogenic diet. Histologically, the aorta predominantly shows lesions of the fatty streaks type with necrotic areas in the deep; the carotid lesions show some lipid in smooth muscle cells disseminated in a sub-endothelial "edematous" space (rich in protein). The cerebral arteries do not show any lesion. At TEM, the aortic lesions look sometimes as advanced plaques with an initial fibrosis at the surface; the carotid lesions are characterized by a granular deposit in the sub-endothelial space in which some smooth muscle cells (with lipid in the cytoplasm) are present; in the cerebral arteries only the presence of collagen fibers among the smooth muscle cells of the media, never observed in the animals fed the atherogenic diet alone, has sometimes been noted.

Natural history of TCDD-induced liver lesions in rats as observed by transmission electron microscopy during a 32-week period after a single intraperitoneal injection.

Forty-two male rats were injected with a single intraperitoneal dose of TCDD in acetone and corn oil and sacrificed after 2, 4, 8, 16, 24, and 32 weeks, to study the long-term effects of a single injection. The liver lesions become progressively worse up to the 16th week and appear thereafter to slowly regress.

An ultrastructural comparison of diet-induced atherosclerosis of arteries supplying the central nervous system in cynomolgus and rhesus monkeys.

The carotid lesions of cynomolgus and rhesus monkeys fed an 8- to 12-months atherogenic diet are very severe. However, the basilar, vertebral and middle cerebral arteries of the same atherosclerotic monkeys look instead, at SEM examination, similar to the control ones. At TEM examination, these arteries of the atherosclerotic monkeys show only minimal lesions in the subendothelial space ('edema' and presence of fragments of basilar membrane) and sometimes necrobiosis of endothelial cells. The smooth muscle cells, which are also present in the controls in these arteries in the subendothelial space, are sometimes surrounded by a nest of basement membrane beads and do not contain lipid droplets.

[Preliminary data on the different endothelial reaction to Con A at different levels of the arterial tree in rabbits and in Cynomolgus monkeys]. / Dati preliminari sulla diversa reazione endoteliale alla Con A, a differenti livelli dell'albero arterioso, nei conigli ed in scimie cynomolgus.

Delayed appearance of atherosclerotic lesions in cerebral arteries has been observed not only in man but also in monkeys and rabbits submitted to atherogenic diets. Previous observations of ours had shown a Con A positive reaction ("glycocalyx" or "surface coat") at the luminal surface and in the plasmalemmal vesicles of aortic endothelial cells of rabbits an other laboratory animals. The "surface coat" is now reputed the site of lipoproteinlipase activity whose importance in atherogenesis has recently been stressed. In our present observations, the endothelial cells Con A reactivity after Bernhard and Avrameas which was not previously studied in the cerebral arteries of rabbits and monkeys has resulted always lacking in this arterial district. Those observations may help explaining delayed appearance of atherosclerotic lesions in cerebral arteries.

Aortic surface coat scanning electron-microscopic modifications after short-term hypercholesterolic diet, visualized in rabbits by con A-haemocyanin reaction.

Modifications of the aortic endothelial surface coat have been visualized at SEM with the use of the Con A-haemocyanin method. After fifteen days of an atherogenic diet, a strong increase of the reactive coat was evident in areas near the orifice of the collateral branches. In other areas, the reaction appeared to be intensely diminished.

Regression of arteriosclerotic lesions in rhesus monkey aortas after regression diet. Scanning and transmission electron microscope observations of the endothelium.

Scanning and transmission microscopy were used to study aortic intima atherosclerotic lesions in Rhesus monkeys during both progression and regression phases. Scanning micrographs of severely atherosclerotic lesions showed areas of disjunctive endothelium and discontinuous basement membranes, frequently accompanied by red blood cells and other circulating elements adhering to the surface. Transmission micrographs also showed occasional areas of endothelial cell damage and loss with lipid-laden smooth muscle cells and foam cells beneath. Regressed lesions (affected by low-fat, low-cholesterol diet with or without cholestyramine) showed endothelial changes suggestive of reparative processes. Scanning micrographs showed flattened residual lesions with continous endothelial lining, while transmission microscopy disclosed interdigitated intercellular tight junctions and frequently reduplicated basement membranes.