Age-related Changes in Rat Myocardium Involve Altered Capacities of Glycosaminoglycans to Potentiate Growth Factor Functions and Heparan Sulfate-altered Sulfation
Abstract
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.
Related
- Hierarchical control of remyelination by heparan sulfate sulfation
- Recent Advances in Protein Tyrosine Sulfation and Its Emerging Roles in Human Diseases
- Synovial fluid glycosaminoglycans signature involved 3-O-sulfated heparan sulfate modulated by TGF-β pathway in OA
- Targeted tumor desialylation by engineered probiotic reprograms the tumor microenvironment to potentiate immunotherapy
- Hopeaphenol targets histidine kinase signaling across kingdoms to suppress bacterial virulence and potentiate plant immunity
BibTeX
@article{huynh2026agerelated,
title = {{Age-related Changes in Rat Myocardium Involve Altered Capacities of Glycosaminoglycans to Potentiate Growth Factor Functions and Heparan Sulfate-altered Sulfation}},
author = {Minh Bao Huynh and Christophe Morin and Gilles Carpentier and Stephanie Garcia-Filipe and Sofia Talhas-Perret and Véronique Barbier-Chassefière and Toin van Kuppevelt and Isabelle Martelly and Patricia Albanese and Dulce Papy-Garcia},
journal = {Journal of Biological Chemistry},
year = {2026},
month = oct,
doi = {10.1074/jbc.m111.335901},
url = {https://hal.science/hal-05801831v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Age-related Changes in Rat Myocardium Involve Altered Capacities of Glycosaminoglycans to Potentiate Growth Factor Functions and Heparan Sulfate-altered Sulfation
AU - Minh Bao Huynh
AU - Christophe Morin
AU - Gilles Carpentier
AU - Stephanie Garcia-Filipe
AU - Sofia Talhas-Perret
AU - Véronique Barbier-Chassefière
AU - Toin van Kuppevelt
AU - Isabelle Martelly
AU - Patricia Albanese
AU - Dulce Papy-Garcia
PY - 2026
DA - 2026/10/15
JO - Journal of Biological Chemistry
DO - 10.1074/jbc.m111.335901
UR - https://hal.science/hal-05801831v1
AB - 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.
SN - 0021-9258
SN - 1083-351X
ER -