Heart failure in elderly individuals is becoming an increasingly critical public health challenge.
On the occasion of World Heart Day, a recent study spotlights a critical molecular pathway linking cardiac aging, heart failure, and inflammation: the HMGB1–SNX3 axis.
The SNX3-HMGB1 interaction may represent a molecular bridge between aging and cardiac vulnerability.
SNX3 is a member of the sorting nexin family that plays a core role in mediating heart failure by directly interacting with HMGB1. This interaction promotes HMGB1’s nuclear-to-cytoplasmic translocation, a process closely linked with maladaptive cardiac remodeling and inflammation.
High Mobility Group Box 1, when released into the cytoplasm and extracellular space, acts as a Damage-Associated Molecular Pattern (DAMP), triggering strong inflammatory responses. This translocation, from nucleus to cytoplasm, is not merely a passive event, but a tightly regulated process, particularly relevant in stress-induced cardiac remodeling.
SNX3-HMGB1 and pathological heart remodeling
Recent data show that Sorting Nexin 3 (SNX3) plays a direct and pathological role in cardiac hypertrophy and heart failure:
- SNX3 expression is upregulated in cardiomyocytes under stress (e.g., isoproterenol exposure) and in pressure-overload heart failure models (TAC in mice, AAC in rats).
- Overexpression of SNX3 accelerates cardiac dysfunction, while cardiac-specific SNX3 knockout protects heart function.
This SNX3-mediated HMGB1 translocation is not just a molecular detail — it’s a crucial driver of inflammation, hypertrophy, and maladaptive remodeling that characterizes heart failure.
In the elderly heart, elevated cytoplasmic and extracellular HMGB1 levels contribute to a pro-inflammatory microenvironment, impairing tissue repair and promoting fibrosis and hypertrophy.
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Read the full article about the study
