Endothelial decorin in cardiac aging: mechanistic ambiguities and therapeutic challenges

Le résumé fourni par la source

We read with great interest the seminal study by Luxán et al.1 which identifies endothelial-cell-derived non-glycanated decorin (DCN) as a critical mediator of cardiac inflammation during aging. The authors provide compelling evidence that non-glycanated DCN activates a pro-inflammatory macrophage phenotype via the EGFR/NF-κB/CCL2 axis, linking vascular aging to myocardial inflammation. While this work substantially advances the field, several mechanistic and translational aspects warrant deeper scrutiny to fully appreciate its implications. A fundamental question remains unresolved: what drives the accumulation of non-glycanated DCN in aging endothelium? The study associates aging with increased non-glycanated DCN but does not elucidate whether its abundance results from impaired glycosylation machinery, endoplasmic reticulum stress, or oxidative damage. Glycosylation is ATP-dependent and relies on enzymatic cascades involving galactosyltransferases (e.g. GALNT2).2 Age-related mitochondrial dysfunction or nutrient-sensing disruptions could compromise these processes, yet the authors do not explore such upstream regulators. If non-glycanated DCN accumulation is merely a passive consequence of global cellular dysfunction, its therapeutic targeting may have limited specificity. Conversely, if it is actively regulated—e.g. via stress-responsive transcriptional programs—it represents a more promising intervention node. Future studies should delineate the molecular triggers, perhaps through proteomic or glycosyltransferase activity profiling in aged endothelial cells.2,3

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.