M. Julian

Identifying arteriosclerosis and aortic atheromatosis by skin biopsy

Summary Photonic and ultrastructural examination of skin biopsies accurately reflect the condition of vascular walls. A normal skin type 0 is the equivalent of normal vessels, while skin types II and III correspond to arteriosclerotic aortic and coronary vessels. The test is primarily valuable to establish whether a premature arteriosclerosis exists. Estimate of skin lipids — total lipids and total sterols — is a diagnostic test which permits us to establish the degree of atheroma of an individual. Levels of these lipids and the degree of atheroma run parallel. By its histological and biological study, skin biopsy can become an accurate test reliably reflecting the condition of the aorta (atherosclerosis and atheromatosis).

Striae: Morphological aspects of connective tissue

The study of 15 abdominal striae in women aged 25 to 57 shows important histological modifications in the skin. The collagen is fragmented and the ground substance is abundant. Fibroblasts are globular, quiescent, and lose all signs of fibrillar secretion. In the light of the recent biochemical data, our results suggest that the striae are the consequence of fibroblastic dysfunction, due to abdominal distension. Comparison with scarred and normal skin indicate that striae are a special entity belonging to the group of connective dystrophies.

Chronic lathyrism. Effect of β aminopropionitrile on the aortic wall in the adult rat

Summary BAPN did not have the same effect in weaning and adult rats. The BAPN was inactive on the aortic wall of adult rat but it induced clinical symptoms and severe aortic partietal lesions in the weaning rat. The explanation of this different lesions was difficult and some hypothesis were discussed. β Aminopropionitrile (BAPN) fumarate affects connective tissue components, particularly collagen and elastin of the aorta and the skin. These facts have been known since 1952, when Ponsetti and Baird induced aortic aneurism in the rat after acute intoxication with “Lathyrus odoratus” seeds. The precise action mechanism of this toxin was not absolutely clear as has been recalled by Kadar et al (1978) in one of her recent publications. In the growing rat, BAPN caused a defect in collagen and elastic synthesis by inhibiting lysine oxydase, an enzyme indispensable for interfibrillar cross-linking ( Bornstein, 1970 ), (Levene et al, 1959) (Page et al, 1966, 1968, 1972) (Wirtschafter et al, 1962) but it can also effect the glycoaminoglycan metabolism ( Bentley et al, 1970 ), (Hosoda et al, 1967), the aortic wall cells, myocytes (Hosoda et al, 1967) ( Julian, et al, 1971 , Julian, et al, 1971 ) endothelial cells ( Pieraggi et al, 1979 ) and cutaneous fibroblasts ( Bouissou et al, 1974 ) (Hosoda et al, 1967) ( Julian et al, 1973 ). In our previous experimentations ( Bouissou et al, 1978 ), ( Julian, et al, 1971 , Julian, et al, 1971 , Julian, et al, 1972 , Julian, et al, 1976 ) with the young weaning rat, chronic administration of BAPN (lg/kg/day for 9 weeks) did not induce aneurism but considerable lesions of the aortic wall : increased endothelial permeability, dedifferenciation of the myocytes in fibromyocytes, proteoglycan diffusion, changes in the elastic network (breaking, fragmentations or complete lysis of fibers) and late fibrosis (Fig. 1). These changes may be intimately related to those of human aortic arteriosclerosis ( Bouissou et al, 1974 ) ( Julian et al, 1973 ). In these different experimental stages, the greatest aortic partietal changes appeared a few weeks after BAPN treatment was stopped, i. e. in adults rats. These findings raised the problem of the effect of this toxic on the mature aortic connective tissue.

Fine structural evidence of increased endothelial permeability in chronic lathyrism

The endothelium of the thoracic aorta of Wistar rats intoxicated with Beta-Aminopropionitrile (BAPN) for 9 weeks was studied. The animals were sacrificed at intervals, from the first to the 9th week of the treatment and 1, 2 and 3 months after the end of the treatment. Changes in the endothelial cells were studied by electron microscopy after staining with uranyl acetate and lead citrate, after impregnation with lanthanum. BAPN increased endothelial permeability, pinocytosis was more active in treated rats than controls, the intercellular junctions widened and cytoplasmic lesions with cell necrosis occurred. These intimal changes were comparable to those observed in man during ageing and in arteriosclerosis.

Chronic lathyrism and atheromatosis in the rat

Temporary chronic administration of Beta-amino-propionitrile (B.A.P.N.) produced morphological and biochemical changes of the aortic wall of rat as well as abnormalities of the plasma lipid levels. A hyperlipidic diet resulted in the blood plasma lipid abnormalities as B.A.P.N. intoxication. Nine weeks of B.A.P.N. followed by 42 weeks of a hyperlipidic diet increased the aortic cholesterol level and induced an atheroma. The diet alone produced only an endothelial lipid overload. The structure of arterial wall played the decisive role in atherogenesis.

Protective effect of pyridinol carbamate in dermal and aortic connective tissue lesions induced by chronic lathyrism.

Summary The use of Beta-amino-propionitrile (BAPN) (lg/Kg/day during 9 weeks) caused in the rat simultaneous changes in aorta and skin and a hight lipid diet given after intoxication during 46 weeks produced an atheroma. In the skin, the collagen tissue was broken, the elastic lamellae disappeared and the fibroblasts presented evidence of injury. These lesions were comparable to those observed in human skin during aging. The addition of Pyridinol Carbamate to BAPN prevented the formation of lesions in aorta and skin and the formation of atheroma after hyperlipidic diet.

Skin cholesterol in ageing rats and experimental atheroma.

Summary The present experiments have shown the following: 1) The levels of skin cholesterol in the rat, like man, are related to age of the animal and to hyperlipoproteinaemia. 2) In experimental atheroma (BAPN : lg/Kg/day and a high fat diet) no relationship exists between the degree of atheroma and the levels of skin cholesterol, in contrast to the situation in man.

Hypothesis on microangiopathy of cutaneous capillaries

Microangiopathy is a more or less pronounced PAS deposit-located exterior to the endothelial cells of the lymphatics and the basal membrane of the capillaries. This lesion, found in various normal and pathological states, has generated numerous pathogenic hypotheses. The presence of microangiopathy in 5 groups of 50 subjects representing five different clinical conditions, subjects over 60 years old or less than 40, diabetics, latent diabetics or patients with severe coronary heart disease, together with microscopic and/or ultrastructural lesions of the connective tissue (fibroblasts, collagen and elastic fibers, ground substance) has enabled us to propose a pathogenic hypothesis applicable to any microangiopathy. The initial change, hereditary or acquired, would be fibroblastic or interstitial. It would be characterized by the accumulation of glycoproteins, proteoglyacans and soluble collagen in the interstitium. Incomplete drainage of these macromolecules would occur around the blood and lymphatic capillaries and manifest itself by a PAS deposit, the hallmark of the microangiopathy.

Long term lathyrism and atherogenic diet in the rat

In the rat, prolonged administration (7 months) of Beta-Amino-propionitrile in association with a hyperlipidic diet caused the formation of widespread pronounced atheroma. The addition of Pyridinol Carbamate during the treatment minimized and retarded the appearance of lipid overload lesions. The histological modifications were found together with an increase in the free cholesterol fraction. These two observations explain the protective role of Pyridinol Carbamate on the wall of the aorta.

Types of aortic aging and degree of atherosclerosis.

Summary Several factors play a role in the pathogenesis of atherosclerosis. Among them, the state of the arterial wall, the composition and concentration of serum lipids and hemodynamic factors playing essentially a localizing role. In this short article, we analyse the different types of aortic aging. By comparison with the lesions induced with Beta-aminopropionitrile (chronic lathyrism) in the aorta of the rat, animal spontaneously and experimentally refractory to atherosclerosis, we can state that the quantity of lipids deposited, that is the stage of atheromatosis, depends on the nature of aortic aging, that is the qualitative structure of the aortic wall.