Lysyl oxidase activity and elastin/glycosaminoglycan interactions in growing chick and rat aortas.

Abstract

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.

Role of the extracellular matrix in age-related modifications of the rat aorta. Ultrastructural, morphometric, and enzymatic evaluations.

“…22 Because it has been demonstrated that integrins are mainly distributed at cell-cell contacts, a reduction in the surface area available for cell-cell interactions might greatly contribute to the fragility of the endothelial lining. In both adult and old animals, moreover, the subintimal space is bigger, sometimes swollen, and generally rich in glycosaminoglycans (visualized as toluidine blue-stained precipitates), 11 which might alter the permeability and the behavior of the intima components. Thickening of the tunica intima and increased amounts of proteoglycans were also observed in aging rabbit aortas without any evidence of extracellular lipid deposition, 23 suggesting that even in this animal model, which is known to frequently develop vascular diseases, a further stimulus in addition to morphological modification is necessary for atherosclerosis development.…”

Biomimetic Regeneration of Elastin Matrices Using Hyaluronan and Copper Ion Cues

“…36,37 Because the physico-chemical and biological properties of HA are often dependent on its size, 38 we have sought to investigate these differences in the context of stimulating elastin matrix synthesis. 16,17 In other studies, copper ions (Cu 2þ ) have been shown to minimize vascular defects, 39 promote angiogenesis, 40 and enhance LOX enzyme activity.…”

“…Moreover, highly anionic GAGs (HA in this case) promote elastic fiber formation by electrostatically binding to the unoxidized lysine residues of newly synthesized tropoelastin during their association with microfibrils, thus preventing their random self-aggregation far away from the site of fiber formation. 36 The retention of the tropoelastin molecules by GAGs would thus indirectly facilitate their LOX-mediated cross-linking and encourage elastin fiber growth, as stated above. In direct support of this hypothesis, the simultaneous availability of HA fragments and increases in LOX synthesis (2.7 AE 0.3 times) with the addition of 0.1 M of CuSO 4 , along with significant presence of fibrillin in the cell layers (as shown in Figure 5), might have contributed to the observed increases in the structural quality of elastin fiber formation.…”

Utility of Hyaluronan Oligomers and Transforming Growth Factor-Beta1 Factors for Elastic Matrix Regeneration by Aneurysmal Rat Aortic Smooth Muscle Cells

“…48 Although LOX can regulate tropoelastin recruitment and crosslinking in this manner, to impact crosslinking efficiency, the extent of crosslink formation itself can be influenced by other factors such as presence of tropoelastinbinding glycosaminoglycans, 49,50 which can locally coacervate tropoelastin molecules at the cell layer to facilitate their crosslinking by LOX. Prior studies have shown that exogenous TGF-b1 augments LOX mRNA expression and activity by healthy cells and thus critically enhances elastin and collagen crosslinking and fiber formation.…”