Lysyl oxidase activity and synthesis of desmosines in cultured human aortic cells and skin fibroblasts: Comparison of cell lines from control subjects and patients with the Marfan syndrome or other annulo-aortic ectasia

Abstract

The activity of lysyl oxidase, the cross-linking enzyme of elastin and collagen, was measured in culture media of human skin fibroblasts, human aortic medial smooth muscle cells (SMCs) and adventitial fibroblasts using [3H]lysine-labelled elastin substrate. In addition, biosynthesis of isodesmosine and desmosine, the cross-linking amino acids of elastin, was studied by metabolic labelling with [14C]lysine and subsequent amino acid chromatography of protein hydrolysates. Lysyl oxidase activity in culture media of skin fibroblasts and aortic smooth muscle cells increased with the growth of the cell population and was at the highest level in cultures of high cell density. Lysyl oxidase activity in the aortic cell cultures was about three times that of skin fibroblasts. Aortic smooth muscle cells synthesized at least 100 times more desmosines than skin or adventitial fibroblasts. No differences were observed in lysyl oxidase activity and synthesis of desmosines between aortic smooth muscle cells or skin fibroblasts from patients with the Marfan syndrome or other annulo-aortic ectasia (dilatation of the ascending aorta) and the corresponding controls.

Increase in the relative level of type V collagen in the placentae of patients with pre-eclampsia

“…The possible cause of changes in the composition of the ECM in the placenta of preeclampsia might involve exposure to hypertension during pregnancy, and an alteration in the density of cells in the human placentae. Recently, cell density-dependent effects have been reported in a number of types of cell, such as mesangial cells (Ishimura et al, 1989;Lermioglu et al, 1991;Worthuis et al, 1993)., vascular smooth muscle cells (Goodman and Majack, 1989;Majors and Ehrhart, 1992), and fibroblasts (Halme et al, 1986;Rösner et al, 1990). It has been suggested that cell density might modulate biological behaviour, causing changes in signal transduction responses to hormonal stimulation, in the growth, synthesis and composition of the ECM, and in the synthesis of specific proteins (Lermioglu et al, 1991;Worthuis et al, 1993).…”

Equal and local-load-sharing micromechanical models for collagens: Quantitative comparisons in response of non-diabetic and diabetic rat tissue

“…Collagen has naturally occurring crosslinks in the form of dehydrohydroxylysinonorleucine [37,38]. Portions of the collagen molecule, not typically crosslinked by lysyl oxidase, however, can become irreversibly crosslinked in the presence of glucose [39][40][41].…”

Elevated expression levels of lysyl oxidases protect against aortic aneurysm progression in Marfan syndrome

“…Early work reported that elastin cross-linking was reduced in the aorta of MFS patients as compared to healthy subjects [14]. However, other studies did not find any significant alteration in LOX activity or LOX mRNA in skin fibroblasts or vascular smooth muscle cells isolated and cultured from MFS patients [15,16]. More recently, defects in collagen microarchitecture (higher collagen content and increased collagen cross-linking), together with increased tissue stiffness have been reported in the aneurysms of MFS mice [17].…”