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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/21147

Title: Cross-linking versus RAGE: How do high molecular weight advanced glycation products induce cardiac dysfunction?
Authors: Deluyker, Dorien
Ferferieva, Vesselina
Noben, Jean-Paul
Swennen, Quirine
Bronckaers, Annelies
Lambrichts, Ivo
Rigo, Jean-Michel
Bito, Virginie
Issue Date: 2016
Citation: International journal of cardiology, 210, p. 100-108
Abstract: BACKGROUND: Several clinical and experimental studies have demonstrated that advanced glycation end products (AGEs) are associated with adverse cardiac outcome. Growing evidence shows that high molecular weight AGEs (HMW-AGEs) might be as important as the characterized low molecular weight AGEs. To date, the role of HMW-AGEs in the pathogenesis of cardiac remodeling remains unknown. In this study, we investigated whether HMW-AGEs are involved in cardiac dysfunction. METHODS: Healthy rats were daily ip injected with 20mg/kg BSA-derived HMW-AGEs or, as a control, unmodified BSA, during 6weeks. Cardiac function was assessed with echocardiography. Plasma levels of glucose, AGEs and soluble RAGE (sRAGE) were measured. AGEs, RAGE and lysyl oxidase (LOX) expression were determined by western blot. RESULTS: After 6weeks, animals displayed a sustained increase in circulating total AGEs without hyperglycemia. HMW-AGEs injections induced cardiac dysfunction characterized by wall hypertrophy, increased heart sphericity, reduced strain and strain rate with preserved ejection fraction. Plasma sRAGE levels were significantly higher compared to control and correlated significantly with decreased strain. RAGE expression, TNF-α and IL-6 remained unchanged. Finally, HMW-AGEs induced prominent cardiac fibrosis associated with an increased LOX expression. CONCLUSION: Our data demonstrate that rather than via a specific activation of RAGE, the deleterious effects of HMW-AGEs are likely mediated via an increased collagen cross-linking responsible for the observed cardiac stiffness. Additionally, we show that in the setting of elevated HMW-AGEs, increased sRAGE levels are markers of altered cardiac function.
URI: http://hdl.handle.net/1942/21147
DOI: 10.1016/j.ijcard.2016.02.095
ISI #: 000372532200024
ISSN: 0167-5273
Category: A1
Type: Journal Contribution
Validation: ecoom, 2017
Appears in Collections: Research publications

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