Preservation of vascular endothelial repair in mice with diet-induced obesity.

INTRODUCTION

Preservation of structural integrity of the endothelial monolayer and maintenance of endothelial cell function are of critical importance in preventing arterial thrombosis, restenosis and atherosclerosis. Obesity has been intimately linked with endothelial dysfunction, and reports of reduced abundance and functional impairment of circulating progenitor cells in obesity have led to the suggestion that defective endothelial repair contributes to obesity-related cardiovascular disease.

METHODS

C57BL/6 mice were fed a high-fat diet for either 3 or 6 months to induce obesity; metabolic phenotyping was then carried out before femoral artery wire injury was performed. Endothelial regeneration was then quantified. Mononuclear cells and myeloid angiogenic cells were cultured and characterized for pro-angiogenic properties.

RESULTS

No impairment of endothelial regeneration following mechanical endothelial injury in diet-induced obese mice when compared with chow-fed controls was observed, despite the induction of an adverse metabolic phenotype characterized by glucose intolerance and insulin resistance. Dietary-obese mice had increased numbers of circulating myeloid angiogenic cells, which retained normal functional properties including intact paracrine angiogenic effects.

CONCLUSION

Preserved endothelial regeneration despite metabolic dysregulation in dietary obese mice suggests that compensatory mechanisms mitigate the deleterious influence of insulin resistance on endothelial repair in obesity.