Galectin-3 Mediates Vascular Dysfunction in Obesity by Regulating NADPH Oxidase 1

Area of Science:

• Cardiovascular Science
• Metabolic Disease Research
• Molecular Biology

Background:

• Obesity is a major risk factor for cardiovascular disease (CVD), with metabolic dysfunction like hyperglycemia contributing to vascular impairment.
• The precise mechanisms linking glucose metabolism to vascular dysfunction in obesity are not fully understood.
• Galectin-3 (GAL3), a lectin upregulated by hyperglycemia, is implicated in CVD, but its causative role requires further investigation.

Approach:

• Investigated the role of GAL3 in microvascular endothelial vasodilation in obesity using GAL3 knockout mice crossed with obese db/db mice.
• Assessed physiological and molecular changes, including oxidative stress markers, endothelial function, hypertension, and NOX1 expression in endothelial cells.
• Utilized endothelial cell-specific GAL3 knockout models and metabolic interventions (muscle mass, insulin signaling, metformin) to confirm findings.

Key Points:

• GAL3 levels were elevated in obese patients and diabetic mouse models.
• GAL3 deletion in obese mice normalized endothelial dysfunction, hypertension, and reactive oxygen species (TBARS).
• Endothelial GAL3 deficiency prevented obesity-induced NOX1 overexpression and associated endothelial dysfunction, mediated by GAL3 oligomerization.

Conclusions:

• Galectin-3 deletion restores microvascular endothelial function in obese mice, primarily via a NOX1-dependent pathway.
• Therapeutic strategies targeting GAL3 and NOX1 may ameliorate obesity-related cardiovascular complications.
• Improvements in metabolic status can reduce pathological levels of GAL3 and NOX1.