Aging Hearts Make Too Much Decorin — and It Triggers Dangerous Inflammation

Cardiovascular disease remains the leading cause of death in Europe, and aging is among its most powerful risk factors. As the heart ages, its structure and function progressively deteriorate — but the molecular signals driving this decline are not fully understood. This study set out to uncover maladaptive mechanisms in the aging heart using a combination of cutting-edge genomic and cellular tools.

Using single-nucleus RNA sequencing, the researchers compared young (3-month) and old (18-month) mouse hearts and identified decorin — a secreted proteoglycan found in the extracellular matrix of endothelial cells — as one of the most significantly upregulated genes with age. This was a notable finding, as decorin has not previously been linked to cardiac aging.

To test decorin's functional role, the team delivered it systemically to young mice via osmotic mini pumps. The results were striking: treated mice developed diastolic dysfunction, increased infiltration of immune cells into the myocardium, elevated IL-1β expression in endothelial cells, and microvascular leakage — all hallmarks of cardiac aging. In cell culture experiments, decorin induced cardiomyocyte hypertrophy and triggered pro-inflammatory cytokine expression through a TLR2-dependent signaling mechanism, while also impairing endothelial barrier function.

The study specifically implicates the non-glycanated form of decorin — lacking its sugar chain modifications — as the biologically active driver of these effects. This distinction matters because different forms of proteoglycans can have very different activities.

These findings open a new line of inquiry into vascular aging and cardiac inflammation. Non-glycanated decorin may represent a druggable target for reducing age-related cardiac deterioration. However, the study is primarily conducted in mice, and whether equivalent mechanisms operate in humans requires further investigation.