# Galectin-3 and the Glyco-Inflammatory Axis: A Missing Link to Residual Cardiovascular Risk in Coronary Artery Disease

## TL;DR

Galectin-3 is identified as a key player in residual cardiovascular risk, linking inflammation and fibrosis in coronary artery disease.

## Contribution

The paper proposes Galectin-3 as a novel therapeutic target for addressing residual cardiovascular risk.

## Key findings

- Elevated Galectin-3 levels correlate with plaque vulnerability and cardiovascular events.
- Inhibiting Galectin-3 reduces inflammation and fibrosis in preclinical models.
- Galectin-3 connects metabolic stress to vascular remodeling and chronic inflammation.

## Abstract

Residual cardiovascular risk remains a major challenge in coronary artery disease, even after optimal lipid-lowering and anti-inflammatory therapy. Beyond classical risk factors, persistent low-grade inflammation and fibrotic remodeling contribute to adverse outcomes that current treatments fail to fully prevent. Growing evidence highlights the glyco-inflammatory axis—the interplay between protein glycosylation-dependent signaling and inflammation—as an underappreciated contributor to residual atherosclerotic risk, largely because current therapeutic strategies do not directly target glycan-mediated mechanisms. Within this framework, Galectin-3 (Gal-3), a β-galactoside-binding lectin, has emerged as a key molecular hub linking metabolic stress, lysosomal dysfunction, and vascular remodeling. By recognizing specific glycan motifs on immune and stromal cells, Gal-3 orchestrates macrophage activation, endothelial dysfunction, and extracellular matrix deposition, thereby amplifying chronic inflammation and fibrosis. Elevated circulating Gal-3 levels are associated with plaque vulnerability and major adverse cardiovascular events, independent of lipid or C-reactive protein levels. Experimental Gal-3 inhibition reduces inflammation and fibrosis in preclinical models, supporting its therapeutic potential. This review integrates mechanistic, translational, and clinical evidence to propose Gal-3 as a missing link between intracellular stress responses and extracellular fibro-inflammatory remodeling. Targeting the Gal-3-mediated glyco-inflammatory axis may represent a novel strategy to overcome residual cardiovascular risk and achieve comprehensive vascular protection in the post-statin era.