Age-related changes in rat myocardium involve altered capacities of glycosaminoglycans to potentiate growth factor functions and heparan sulfate-altered sulfation.
Publication year
2012Source
Journal of Biological Chemistry, 287, 14, (2012), pp. 11363-73ISSN
Publication type
Article / Letter to editor
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Organization
Nephrology
Biochemistry (UMC)
Journal title
Journal of Biological Chemistry
Volume
vol. 287
Issue
iss. 14
Page start
p. 11363
Page end
p. 73
Subject
NCMLS 3: Tissue engineering and pathology N4i 4: Auto-immunity, transplantation and immunotherapy; NCMLS 3: Tissue engineering and pathology ONCOL 3: Translational researchAbstract
Glycosaminoglycans (GAGs) are essential components of the extracellular matrix, the natural environment from which cell behavior is regulated by a number or tissue homeostasis guarantors including growth factors. Because most heparin-binding growth factor activities are regulated by GAGs, structural and functional alterations of these polysaccharides may consequently affect the integrity of tissues during critical physiological and pathological processes. Here, we investigated whether the aging process can induce changes in the myocardial GAG composition in rats and whether these changes can affect the activities of particular heparin-binding growth factors known to sustain cardiac tissue integrity. Our results showed an age-dependent increase of GAG levels in the left ventricle. Biochemical and immunohistological studies pointed out heparan sulfates (HS) as the GAG species that increased with age. ELISA-based competition assays showed altered capacities of the aged myocardial GAGs to bind FGF-1, FGF-2, and VEGF but not HB EGF. Mitogenic assays in cultured cells showed an age-dependent decrease of the elderly GAG capacities to potentiate FGF-2 whereas the potentiating effect on VEGF(165) was increased, as confirmed by augmented angiogenic cell proliferation in Matrigel plugs. Moreover, HS disaccharide analysis showed considerably altered 6-O-sulfation with modest changes in N- and 2-O-sulfations. Together, these findings suggest a physiological significance of HS structural and functional alterations during aging. This can be associated with an age-dependent decline of the extracellular matrix capacity to efficiently modulate not only the activity of resident or therapeutic growth factors but also the homing of resident or therapeutic cells.
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- Academic publications [238441]
- Electronic publications [122508]
- Faculty of Medical Sciences [90373]
- Open Access publications [97504]
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