Alterations of elastin fibrogenesis by inhibition of the formation of desmosine crosslinks. Comparison between the effect of beta-aminopropionitrile (βAPN) and penicillamine

Experimental lathyrism was induced by feeding newborn chicks a diet containing 0.2 and 0.4% DL-Penicillamine, with or without CuSO4 (10 mg/Kg diet) and Vitamin B6 (100 mg/Kg diet), or 0.015 and 0.1% beta-aminopropionitrile fumarate (βAPN). After 7, 15, 25 and 55 days of treatment the animals were killed, the aortas removed and processed for electron microscopy in the presence of markers for proteoglycans, and the elastic fibers were carefully examined. Penicillamine, which prevents the formation of desmosine crosslinks by binding to precursors, induced the production of numerous new elastin fibers which appeared normal from the ultrastructural point of view. It seems, therefore, that at least in chick aortas, desmosine crosslinks are not necessary for the aggregation of tropoelastin molecules into structurally normal fibers. On the contrary, βAPN, a classical inhibitor of lysyl oxidase, induced the tropoelastin molecules to aggregate into abnormal protuberances on the old fibers. Moreover, the elastin deposited during βAPN treatment was always permeated by cytochemically revealed proteoglycans, which were never observed after penicillamine treatment. It is speculated that, at least in the system under study, the e-amino groups of tropoelastin molecules may offer the binding sites for matrix proteoglycans until they are removed by lysyl oxidase, and that matrix proteoglycans might play a role in elastin fibrogenesis by preventing spontaneous tropoelastin aggregation in areas far from growing elastin fibers. © 1985 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.