[Cross antigenicity between human arterial tissue and various germs]. / Antigénicité croisée entre le tissue artériel humain et divers germes.

Cross antigenicity was demonstrated between human arterial tissue and enterobacteriaceae, some streptococcus strains or some viruses, using the indirect immunoenzymatic test. Absorption of antigerm antisera by the glycoproteins of either the human serum or aorta suggested that a glycoprotein or some fragment of it acted as a target-antigen or target-epitope for the investigated antibodies and that these antibodies might attack human arterial tissue.

[Experimental immune arteriosclerosis in the rabbit. Immunogenic and pathogenic properties of glycoproteins and elastins in arterial tissue]. / Artériosclérose expérimentale immune du lapin. Pouvoir immunogène et pathogène des glycoprotéines et élastines du tissu artériel.

Rabbits immunized with kappa elastin produced arteriosclerosis and antibodies that bound to target-structures (elastic fiber sheaths, endothelial and smooth muscle cells). These antibodies were cytotoxic for cultured rabbit or rat arterial smooth muscle cells. Absorption of the antielastin antiserum with pig aorta or human serum glycoproteins inhibited its binding to target-structures and suppressed its in vitro cytotoxicity. These data are discussed.

[Possible intervention of immune mechanisms in the genesis and course of human atherosclerosis]. / Possible intervention de mécanismes immuns dans la genèse et l'evolution de l'athérosclérose humaine.

Aortas, coronary and carotid arteries from 31 patients who died of myocardial or cerebral infarction were examined by direct immunoenzymatic tests (using peroxidase-labelled anti human IgG sheep Fab or anti human complement sheep IgG) and compared to those of 9 patients who died of non atherosclerotic diseases. Immunoglobulins and complement bound to all atherosclerotic lesions, all elastic fiber alterations, all lipid infiltration in patients who died of atherosclerosis, as well as in patients who died of various other causes. Binding was generally more intensive in patients who died of atherosclerosis and in arteries irrigating infarcted areas. These data are discussed.

[Experimental immune arteriosclerosis of rabbits. Immunoenzymatic study]. / Artériosclérose expérimentale immune du lapin. Etude immunoenzymatique.

The immunization of rabbits with aorta homogenates, constituants of the arterial tissue, serum glycoproteins, or lipopolysaccharides from enterobacteria, leads to the production of cross-reacting antibodies and to identical arteriosclerotic lesions. The incubation of aortic slices with anti-rabbit IgG sheep Fab, or anti-rabbit complement sheep IgG, labelled with peroxidase, shows that IgG and complement are bound on prenecrotic cells and on sheaths of elastic fibers. The binding sites are the same, whatever the immunizing agent. The antigenic site blockade prevents the response. The indirect immunoenzymatic test, performed on aortic slices of young control rabbits, shows that the different immune sera obtained with the various antigens bind on the same arterial structures, that is the sheath of elastic fibers, the cellular membrane and cytoplasm. The response to this test is clearly decreased, if not suppressed, by absorption of the immune sera with one of the three following sugars: mannose, NA glucosamine, and sialic acid. These data confirm that the arteriosclerosis induced in the rabbit by immunization is actually of an immune nature and show that the antibodies thus formed are bound on the same arterial structures, independently of the immunizing agent. They suggest that the sugars could be haptens, taking part in cross-reactions and antibody binding.

In vitro immune aggression against rabbit aortic smooth muscle cells.

Rabbit aortic smooth muscle cells cultivated with certain antisera underwent growth changes and necrosis. These cytotoxic antisera were obtained by immunizing rabbits against rat aorta, human or pig aortic glycoproteins, human serum glycoproteins and E. coli lipopolysaccharide. These different antigens share some biochemical characteristics, and contain four main amino acid residues (Glu, Ala, Asp, Gly) and four sugars (mannose, galactose, glucose, N-acetyl glucosamine). The cytolytic properties of these antisera, however, probably correspond to structural analogies, since although ovalbumin is a glycoprotein, anti-ovalbumin antiserum was not cytotoxic. Antibody cytotoxicity against rabbit arterial smooth muscle cells may depend on the biochemical structure of the antigen used to produce antiserum.

Rheumatic-like carditis induced in rabbits by cross-reacting antigens: Streptococcus A polysaccharide and rabbit aortic glycoproteins.

A rheumatic-like carditis was induced in rabbits by 8 mo of immunization with small doses of Streptococcus A polysaccharides or peptoglycane and rabbit aortic glycoprotein. Cardiac lesions were detected 5 to 6 mo after the beginning of immunization and were preceded by the appearance of circulating antibodies. The immunopathological study with peroxidase-labeled antibodies indicated the binding of IgG and C3 complement to the damaged cardiac areas. Enzyme-labeled antibodies to streptococcal polysaccharides were bound to the connective tissue of the cardiac valves and the coronary vessels. An immunological cross-reactivity was detected between Streptococcus A polysaccharide and aortic glycoprotein; this suggests that the immunopathological process initiated by the streptococcal infection may subsequently involve the cardiac tissue itself.

[Behaviour of the aortic lipoidosis in rats twenty months after stopping of an hyperlipidic diet (author's transl)]. / Devenir de la lipoïdose aortique du rat vingt mois après l'arrêt d'un régime hyperlipémiant.

48 rats were placed on an hyperlipidic diet (cholesterol, cholic acid, cholin, propylthiouracil), 23 were sacrificed at various intervals from the fourth up to the twelve month of the experiment. In the remaining 25 rats, the atherogenic regimen was replaced by a normal one. These animals were sacrificed one to twenty months after stopping of the experimental diet. Aortae of experimental and control animals were studied by means of histological and histochemical technics. All the animals developed hypercholesterolemia together with intima and media lipoidosis. None demonstrated any aortic cell proliferation. The only metabolic change of the smooth muscle cell was a progressive decrease in 5' nucleotidase, acid esterase and cholinesterase activities. The return to a normal diet involved the reversion of the serum cholesterol level to normal values and the disappearance of intima lipoidosis. The reduced enzymatic activities in the media returned to normal levels around the sixth month. The surfaces of the extracellular sudanophilic areas decreased. However, twenty months after stopping of the atherogenic diet, some lipids still persisted at the edges of the elastic fibres.

A comparative study of the arterial tissue metabolism in atherosensitive and atheroresistant species. I. Comparison between rabbit and rat aortas.

Twenty eight enzymatic activities and four macromolecular substances have been histochemically compared in rat and rabbit aortas, embedded in a common block. The study was carried out at different stages of development: 3 days, 3 months, 7-9 months and 17-19 months. In addition, lipase and cholinesterase were biochemically assayed in adult rat and rabbit aortas. The rat aortas (atheroresistant) had a better supply of aerobic oxidoreductases [linked to the pentose pathway (G6PD, 6PGD) as well as to the Krebs cycle (SD, ICD)], lipolytic enzymes (acid esterases, cholinesterase, lipase), lysosomal enzymes (acid PH/ase, Aryl-sulf/ase - Betaglu/ase), ADPase - ATPase - AlK Ph/ase Alpha GPD and acid lipids. Rabbit aortas (atherosensitive) were richer in metachromatic GAG, UDPGD (GAG Anabolism), glycogen, and related enzymes (phosphorylase, glycogen synthetase) as well as 5'-nucleotidase, Beta HBD, Lactate D and Aldolase. These differences support the hypothesis that arterial atherosensitivity is related to the activity and efficiency of smooth muscle cell energetic and catabolic processes, which govern the behaviour of lipids, proteins and carbohydrates as they penetrate the arterial wall. The factors that determine the proliferative and sclerogenic responses of arterial tissues to aggressions and, in particular, the response to lipids, remain, however, to be determined.

[Prolonged probucol treatment in patients with cardiovascular diseases (author's transl)]. / Administration prolongée de probucol chez des malades atteints d'affections cardio-vasculaires.

Thirty five patients with cardiovascular diseases and hypercholesterolemia were treated with probucol and a low-fat diet for 12 to 50 months. The mean serum cholesterol level decreased from 327,2 to 279,4 mg/dl (- 14,6% p. < 0,001). Probucol lowered the plasma cholesterol level by about the same extent in primary hypercholesterolemia type IIa (10 patients) and in combined hypercholesterolemia type IIb or III (23 patients). No interaction was observed between probucol and other drugs prescribed for cardiovascular diseases particularly antivitamin K and diuretics. No variation in liver and renal function tests, in glucose level, blood count or body weight were noted. The E.C.G. was not modified by treatment. The therapy was withdrawn in one patient because of diarrhea.

[Behaviour of the aortic lipoidosis in rats twenty months after the withdrawal of an hyperlipidic diet (author's transl)]. / Devenir de la lipoïdose aortique du rat vingt mois après l'arrêt d'un régime hyperlipémiant.

48 rats were placed on an hyperlipidic diet (cholesterol, cholic acid, cholin, propylthiouracil), 23 were sacrificed at various intervals from the fourth up to the twelve month of the experiment. In the remaining 25 rats, the atherogenic regimen was replaced by a normal one. These animals were sacrificed one to twenty months after the withdrawal of the experimental diet. Aortae of experimental and control animals were studied by means of histological and histochemical technics. All the animals developed hypercholesterolemia together with intima and media lipoidosis. None demonstrated any aortic cell proliferation. The only metabolic change of the smooth muscle cell was a progressive decrease in 5' nucleotidase, acid esterase and cholinesterase activities. The return to a normal diet involved the reversion of the serum cholesterol level to normal values and the disappearance of intima lipoidosis. The reduced enzymatic activities in the media returned to normal levels around the six month. The surfaces of the extracellular sudanophilic areas decreased. However, twenty months after the withdrawal of the atherogenic diet, some lipids still persisted at the edges of the elastic fibres.

Experimental nephropathy induced in rabbits by immunization with Escherichia coli 055 lipopolysaccharide. 2. Immunologic findings.

Thirty-seven rabbits were immunized against lipopolysaccharide from Escherichia coli or Salmonella enteritidis over a period of up to 16 months. The animals developed antibodies against rabbit renal glycoproteins and against bacterial polysaccharide; they also showed signs of kidney lesions. The immunoperoxidase test showed antibody and complement (C3) fixation on the periphery of glomeruli and tubules. Antibodies extracted from the kidneys of the immunized animals reacted with isologous and autologous renal glycoproteins, suggesting that the renal lesions were due to an immunologic response. The cross-reactivity between the bacterial lipopolysaccharide and the renal glycoproteins appears to be responsible for these lesions.

Cartilage and bone formation in arterial wall. 2. Ultrastructural patterns.

The ultrastructural aspects of cartilaginous and osseous foci developed in aorta of rabbits immunized against rat aorta homogenates was studied. Besides normal and modified smooth muscle cells, various types of transformed mediacytes were observed in and around these foci: some of them resembled connective and young mesenchymatous cells, others had the appearances of cartilaginous and osseous cells. The possible role of the modified (multipotential) smooth muscle cells in aortic chondro- and osteogenesis is considered in some cases. Following histogenetic pathway is suggested: s.m.c. leads to modified s.m.c. lead to young mesenchyme-like cells ("inducible osteogenic precursor cells") leads to "chondro-mediacytes", "osteomediacyte".

[Spontaneous aortic lesions in the rabbit. Possible role of immune mechanisms]. / Etude des lésions aortiques spontanées du lapin. Rôle possible de mécanismes immuns.

The incidence of spontaneous arteriosclerosis, studied in 493 rabbits, increased with ageing. Various evidences suggested the immune nature of these lesions : 1. The direct immunoperoxidase test showed the binding of both rabbit IgG and complement on injured areas, while in apparently normal structures of the same aortas (endothelium and elastic fibers) this binding occurred in some areas with only IgG. 2. The indirect immunoperoxidase test demonstrated the binding of the gammaglobulins from rabbits with spontaneous arteriosclerosis to the aortic structures of normal young rabbits (myocytes, endothelial cells and elastic fibers). The previous demonstration of a cross-antigenicity between aortic glycoproteins and E. coli lipolysaccharides on the one hand, the positivity of delayed hypersensitivity reactions against E. coli lipopolysaccharides in rabbits with spontaneous aortic lesions on the other, led to the hypothesis that lipopolysaccharides antibodies might both bind and injury some aortic structures.

Cartilage and bone formation in arterial wall. 1. Morphological and histochemical aspects.

Cartilaginous and/or osseous foci were observed in eight aortas from 20 rabbits immunized against heterologous aorta homogenates and sacrificed 11 to 24 months later. They were studied by means of histological and histochemical methods and compared with normal aortas, cartilage and bone. Some of the observed changes seemed to be true markers of these transformations. Chondroid metaplasia was characterized by 1) generalized increase in alcianophilic hyaluronidase sensitive substances. 2) Appearance of Dermatan and/or Keratan sulfates round some isolated cells. 3) Advent of G6 Pase and Alk. Phase activities in cells adjacent to osseous foci. Osteous metaplasia was characterized by 1) decrease, then disappearance of alcianophilic and PAS positive material, 2) increase in osteoblastic alkaline Pase-activities.

[Morphological and histochemical behavior of arterial tissue in normal and spontaneously hypo- or hypercholesterolemic rats on a normal or hyperlipidic diet]. / Comportement morphologique et histochimique du tissu artériel de rats génétiquement normo, hypo et hypercholestérolémiques à l'état normal et après régime hyperlipémiant.

Hypo and hypercholesterolemic rats strains were selected (Lyon) and compared to a normocholesterolemic one issued from the same race (Sprague-Dawley). The arterial tissue of these three strains at three ages (10-19-25 months) and their reactivity to an hyperlipidic diet (2 and 6 month duration) were studied using histological and histochemical technics. There were neither histological nor histochemical differences between the three strains whatever the ages. Therefore, at the present stage of selection, the genetic differences have not changed the arterial metabolism or its evolution during ageing. However the arterial reactivity of hypo and hypercholesterolemic strains towards an hyperlipidic diet was different: indeed both strains developed hypercholesterolemia, liver steatosis and diffuse intimal lipoidosis, but on the other hand the hypercholesterolemic rat alone demonstrated arterial cell proliferation. These data suggest that a same genetic trait can give rise to both a spontaneous hypercholesterolemia and an arterial hyperactivity against a superimposed hyperlipemia.

Experimental nephropathy induced in the rabbit by immunization with a lipopolysaccharide from Escherichia coli.

Twenty rabbits were each injected with 100 microgram of lipopolysaccharide from Escherichia coli 055 at weekly intervals for up to 15 months. The antisera showed an immunologic cross-reactivity with rabbit kidney glycoprotein. A macroscopic nephropathy was present in 14 of the 17 rabbits in which the kidneys were examined. All the rabbits showed extensive histologic lesions involving all the structures of the kidney: organized thrombosis of the arteries, extensive areas of infarction, glomerular atrophy, tubular necrosis and proliferation of young connective tissue. A marked infiltration with lymphoid cells and some plasmacytes was present. The immunologic character of this nephropathy and the immunopathogenic mechanism involved in its pathogenesis are discussed.

[Early histochemical aging of arteries submitted to constant physical stress]. / Senescence histochimique précoce d'artères soumises aux stress physiques constants.

The hemodynamic stress effect on the tissue metabolism of coronary and splenic arteries was histochemically and comparatively studied in beagle dogs 6 months, 1 and 8 years-old. The results indicated that more than 30 enzyme activities (EA) studied are similar in both vessels in the young animal (6 months). During ageing (1--8 years old dogs) the EA linked to aerobic oxydo-reduction, ATP hydrolysis and estero-lipolysis decreased in the coronary arterial wall; conjointly the lysosomal acid phosphatase increased. Splenic artery EA remained unchanged during this period. These data suggest that repeated hemodynamic injuries may accelerate aging of the coronary artery by early perturbations of EA linked to oxydoreduction and to lipolytic power of the arterial smooth muscle cells.

Segmental differences in morphogenetic activity of arterial smooth muscle cells. Histochemical and radioautographic studies.

Differences in morphogenetic and metabolic activities of the arterial smooth muscle cells (s.m.c.) of the young rat's aorta and femoral artery were studied by histochemical, radiochemical and quantitative radioautographic methods. 3H-proline was found to be incorporated into the medial myocyte of both vessels and released into the extracellular connective tissue matrix during the first 6 hours. The intracellular and extracellular phases of this process were similar to those of other scleroprotein-synthesizing cells. The 3H-proline incorporation, the metachromasia (GAG) and the activities of acetyl-cholinesterase, beta-glucuronidase, aryl-sulfatase and 5'-nucleotidase were more intense in the aortic media. On the other hand, some oxido-reductases linked with cellular respiration, glycogenolysis and energy production as well as the myosin-ATPase and MAO activities are more intense in the femoral artery. These differences suggest the morpho-functional diversity of the arterial s.m.c.: greater morphogenetic activity of the aortic myocyte; earlier and higher contractile differentiation of the femoral one.