Soluble Receptor for Advanced Glycation End-products regulates age-associated Cardiac Fibrosis
| Autor: | Calogero C. Tedesco, Fabrizio Veglia, Giovanni Pezone, Marco Bianchi, Francesco Scavello, Giulio Pompilio, Federica Macrì, Gualtiero I. Colombo, Estella Zuccolo, Stefania Castiglione, Alessandro Scopece, Giuseppina Milano, Laura Popolo, Angela Raucci, Patrizia Nigro, Elisa Gambini, Filippo Zeni, Genny Degani |
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| Přispěvatelé: | Scavello, F., Zeni, F., Milano, G., Macri, F., Castiglione, S., Zuccolo, E., Scopece, A., Pezone, G., Tedesco, C. C., Nigro, P., Degani, G., Gambini, E., Veglia, F., Popolo, L., Pompilio, G., Colombo, G. I., Bianchi, M. E., Raucci, A. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cardiac function curve
medicine.medical_specialty Aging Cardiac fibrosis Receptor for Advanced Glycation End Products heart failure Heart failure Applied Microbiology and Biotechnology RAGE (receptor) Cell Line Transforming Growth Factor beta1 SRAGE Mice Fibrosis Glycation Internal medicine medicine Animals Humans Protein Isoforms Receptor Molecular Biology Ecology Evolution Behavior and Systematics Cardiac remodeling business.industry Myocardium fibrosis Cell Biology Fibroblasts medicine.disease Actins Mice Inbred C57BL Endocrinology cardiovascular system Female cardiac remodeling business Developmental Biology Transforming growth factor Research Paper sRAGE |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| Popis: | Myocardial aging increases the cardiovascular risk in the elderly. The Receptor for Advanced Glycation End-products (RAGE) is involved in age-related disorders. The soluble isoform (sRAGE) acts as a scavenger blocking the membrane-bound receptor activation. This study aims at investigating RAGE contribution to age-related cardiac remodeling. We analyzed the cardiac function of three different age groups of female Rage-/- and C57BL/6N (WT) mice: 2.5- (Young), 12- (Middle-age, MA) and 21-months (Old) old. While aging, Rage-/- mice displayed an increase in left ventricle (LV) dimensions compared to age-matched WT animals, with the main differences observed in the MA groups. Rage-/- mice showed higher fibrosis and a larger number of α-Smooth Muscle Actin (SMA)+ cells with age, along with increased expression of pro-fibrotic Transforming Growth Factor (TGF)-β1 pathway components. RAGE isoforms were undetectable in LV of WT mice, nevertheless, circulating sRAGE declined with aging and inversely associated with LV diastolic dimensions. Human cardiac fibroblasts stimulated with sRAGE exhibited a reduction in proliferation, pro-fibrotic proteins and TGF-beta Receptor 1 (TGFbR1) expression and Smad2-3 activation. Finally, sRAGE administration to MA WT animals reduced cardiac fibrosis. Hence, our work shows that RAGE associates with age-dependent myocardial changes and indicates sRAGE as an inhibitor of cardiac fibroblasts differentiation and age-dependent cardiac fibrosis. |
| Databáze: | OpenAIRE |
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