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Abstract. Hydrophobic tropoelastin molecules aggregate in vitro in physiological conditions and form fibers very similar to natural ones (Bressan, G. M., I. Pasquali Ronchetti, C. Fornieri, E Mattioli, I. Castellani, and D. Volpin, 1986, J. Ultrastruct. Molec. Struct. Res., 94:209-216). Similar hydrophobic interactions might be operative in in vivo fibrogenesis. Data are presented suggesting that matrix glycosaminoglycans (GAGs) prevent spontaneous tropoelastin aggregation in vivo, at least up to the deamination of lysine residues on tropoelastin by matrix lysyl oxidase.Lysyl oxidase inhibitors beta-aminopropionitrile, aminoacetonitrile, semicarbazide, and isonicotinic acid hydrazide were given to newborn chicks, to chick embryos, and to newborn rats, and the ultrastructural alterations of the aortic elastic fibers were analyzed and compared with the extent of the enzyme inhibition. When inhibition was >65 % all chemicals induced alterations of elastic fibers in the form of lateral aggregates of elastin, which were always permeated by cytochemically and immunologically recognizable GAGs. The number and size of the abnormal elastin/ GAGs aggregates were proportional to the extent of lysyl oxidase inhibition. The phenomenon was independent of the animal species. All data suggest that, upon inhibition of lysyl oxidase, matrix GAGs remain among elastin molecules during fibrogenesis by binding to positively charged amino groups on elastin. Newly synthesized and secreted tropoelastin has the highest number of free epsilon amino groups, and, therefore, the highest capability of binding to GAGs. These polyanions, by virtue of their great hydration and dispersing power, could prevent random spontaneous aggregation of hydrophobic tropoelastin in the extracellular space.

Connective tissues such as blood vessels are known to be greatly affected by age because of impaired functional properties and increased susceptibility to diseases. With the aim of providing further information on the role of the extracellular matrix in age-related modifications, we investigated the aorta in the rat model from birth to senescence by means of morphological and morphometric observations and by evaluation of lysyl oxidase activity. Results focused on the dramatic vascular rearrangements due to progressive fibrosis of the extracellular matrix and on prominent elastin modifications. The presence of lysyl oxidase activity, even in the oldest animals, might be at least partly responsible for the increased stiffness of the aging extracellular matrix. The striking age-related remodeling of the aortic architecture and the alterations of the interactions between cellular and extracellular compartments might greatly influence the functional properties of the arterial wall in senescence, at least contributing to the consequences of some apparently age-related vascular disorders. ( integrated system composed of collagen fibrils, elastic lamellae, proteoglycans, minor collagens, and structural glycoproteins that, together with cells, guarantees the major properties of the vascular compartment, i.e., the diffusion at proper rates of nutrients and other metabolic factors through optimal blood flow. -4Apart from calcifications, fibrosis, and atheromatous lesions, which are frequently observed in the vessel wall of several species 5 " 9 and which are at least partly responsible for the failure of the cardiovascular system with age, 7 little is known about the pathogenesis of the age-related modifications of the vessel wall, which may affect vascular properties such as elasticity and resilience and which may be of paramount importance in understanding specific pathological conditions. The present work was undertaken with the aim of focusing attention on the age-related modifications of the aortic arch in rats from birth to senescence. Qualitative and quantitative morphological data concerning the structure and distribution of the cellular and extracellular components were correlated with the activity of lysyl oxidase, the enzyme that catalyzes the formation of collagen and elastin cross-links and therefore contributes to the stabilization of these two polymers. Supported by Fondi (40%) and Ministero Universita e Ricerca Scientifica e Technologica (60%).Address for correspondence: Prof. C. Fornieri, 1st. Patologia Generale, Via Campi 287, 41100 Modena, Italy.Received April 21, 1992; accepted May 13, 1992. In the light of our results, we suggest that the interactions of the cellular and the extracellular compartments and the ratio between collagen and elastin play key roles in conditioning the morphological-functional properties of the arterial wall and, therefore, explain at least some of the consequences (although not the pathogenesis) of several pathological processes affecting the vascular compartment with inc...

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