Production of Atherosclerosis in Lathyritic Aortas of Rats

Electron-microscopic examination of aortas of rat treated orally and chronically with β-aminopropionitrile (BAPN) has shown progressive lesions in the elastic framework. This is associated with modifications of cells in the media which dedifferentiate into histiocytes and fibrocytes and also multiply. These changes begin in the 5th week of treatment, and are responsible for the hyperplasia of the intima as well as its thickening and collagenization. They support observations made in man during aortic aging, namely with regard to the intima and the intima-media junction. A high lipid diet given at various times during intoxication causes lipid deposition in the intima and a substantial penetration into the media when the lesions are developing. This also corroborates some hypotheses on the development of human atheroma. The addition of pyridinol carbamate (PDC) to BAPN prevents the formation of elastic tissue lesions. When given after the cessation of lathyrism treatment, PDC arrests and causes regression of lesions in the aortic media. It has no effects on lipid deposits, but the deposits are confined to the intima only.

Section: Discussionsupporting

confidence: 89%

Aortic Lathyrism: Ultrastructural Study of Lesions in the Aortic Wall and the Protective Effect of Pyridinol Carbamate

Pieraggi¹,

Julián²,

Bouissou³

1974

“…Il est remplacé par un matériel fibrillaire disposé en tous sens, séparant les cellules musculaires en hyperplasie. Hosoda et Susuki [15] furent les premiers, à notre connaissance, à mentionner cette lésion que d'autres considèrent comme une réparation active de la média par prolifération des myocytes après dislocation de la charpente élastique par le BAPN. Rat No.…”

Section: Modifications Pariétales De L'aorte1unclassified

“…On peut dès lors émettre l'hypothèse qu'à la suite d'un lathyrisme chronique l'aorte pourrait devenir Fig. 10 fibreuse, ses cellules musculaires dédifférenciées élaborant des fibres colla gènes et perdant leur pouvoir, comme Hosoda et Susuki [15] l'avaient suggé ré, de maintenir l'intégrité des fibres élastiques restantes.…”

Section: Déductionsunclassified

“…En second lieu, cette intoxication peut rendre possible une étude plus détaillée des transformations structurales des cellules musculaires, étude qui renforcerait l'hypothèse biochimique soulevée par Hosoda et Susuki [15] que les cellules musculaires de la média contrôlent le métabolis me du collagène et de l'élastine. Ce sont ces deux aspects que nous envisa geons après avoir rappelé le vieillissement parallèle des tissus conjonctifs dermique et aortique humains.…”

unclassified

See 1 more Smart Citation

Lathyrisme chronique

Julián¹,

Pieraggi²,

Bouissou³

1973

In man, a parallelism between the sub epidermic connective tissue and the vascular (aorta and coronary) changes with age was noted. The vascular state is reflected by the alterations of the papillary dermis – normal vessels correspond to a normal skin, what ever the patient’s age; a damaged aorta and coronary artery correspond to a damaged skin. The study of the cutaneous fibroblasts during human ageing reveals a progressive lack of microfibrillar secretions and signs of cytoplasmic suffering. The more intense the vascular injury, the more pronounced is the cutaneous change. The detection of the subepidermic connective tissue injuries is particularly interesting for the diagnosis of early arteriosclerosis. Above age 45, vascular and cutaneous alterations increase. They are linked to normal ageing. This parallelism between vascular ageing and the degree of the cutaneous damage also appears in chronic lathyrism. In the rat, the administration of lathyric toxic agents at weak and prolonged doses caused simultaneous alterations of aortic and cutaneous connective tissues in the eighth week of intoxication. In the aorta, a dislocation of the elastic framework, an increase of the interstitial tissue, a dedifferentiation of muscle cells are observed. In the skin, the papillary dermis presents a collagenic tissue with thin and fragmented bundles, a progressive disappearance of the elastic framework and alterations of the fibroblasts with signs of damage and a deficient secretion. In experimental lathyrism, the changes of the elastic fibres are accompanied by a dedifferentiation of the muscular cells of the aorta and an alteration of the cutaneous fibroblasts. These damages correspond to the modifications observed during ageing in man. This experimentation reveals chronic lathyrism as an experimental pattern of the human connective tissue ageing. This toxic agent causes connective tissue (fibrillary and cellular), aortic and cutaneous injuries rather similar to those observed in senescent man.

“…The diet alone only produced an endothelial lipid overload and increased the aortic cholesterol level but less than BAPN and hyperlipidic diet together. Addition of metformin to BAPN prevented the formation of atheromatous lesions in the aorta and minimized the level of lipids in the aortic wall and of the dermis.In the spontaneously and experimentally atheroresistant rat, /3-aminopropionitrile fuma rate (BAPN) induced aortic wall lesions (27) which were characterized by alterations of the endothelium cells and of the elastic fibers, penetration of proteoglycans, changes of smooth muscle cells into fibromyocytes and, later on, fibrosis (4,5,13,25).Pronounced atheromatous lesions were in duced in the rat by chronic intoxication with 1 With the technical help of Mrs. Foulquier, Mr. Deloly and Miss Blavignac. BAPN (9 weeks) followed by a prolonged ath erogenic diet (10 months) (8,15,17,25).…”

mentioning

confidence: 99%

Chronic Lathyrism and Atheromatosis in the Rat Protective Effect of Metformin

Bouissou¹,

Thiers²,

Douste-Blazy³

et al. 1980

Chronic administration of β-aminopropionitrile fumarate (BAPN) (1 g/kg/day for 9 weeks) produced morphological changes of the aortic wall and in dermis, and biochemical changes of the aortic wall in the rat. Chronic administration of BAPN did not produce plasma lipid abnormalities such as those due to hyperlipidic diet. 9 weeks of BAPN followed by 10 months of a hyperlipidic diet increased the aortic cholesterol level and induced atheroma. The diet alone only produced an endothelial lipid overload and increased the aortic cholesterol level but less than BAPN and hyperlipidic diet together. Addition of metformin to BAPN prevented the formation of atheromatous lesions in the aorta and minimized the level of lipids in the aortic wall and of the dermis.