Adiponectin Fails in Improving Angiogenic Repair in Streptozocin-Treated or Leprdbdb Mice after Hind Limb Ischemia

Abstract EN

Objectives.

Type 1 and 2 diabetes carry risk factors for the development of microvascular diseases with associated impairment of angiogenic repair.

Here, we investigated whether adiponectin, an adipocyte-specific adipocytokine with antiatherosclerotic and antidiabetic properties, regulates angiogenic repair in response to tissue ischemia in Leprdb/db and streptozocin-treated diabetic mouse models.

Methods.

Adenoviral vectors containing the gene for β-galactosidase, full-length mouse adiponectin, and dominant-negative AMPKα2 were used in streptozocin-treated male Leprdb/db mice, after which hind limb blood flow was measured using a laser doppler blood flow analyzer.

Results.

The angiogenic repair of ischemic hind limbs was impaired in both streptozocin-treated and Leprdb/db mice compared to wild-type mice as evaluated by laser doppler flow and capillary density analyses.

Adenovirus-mediated administration of adiponectin accelerated angiogenic repair after hind limb ischemia in WT mice, but not in Leprdb/db mice or mice treated with streptozocin.

In vitro experiments using HUVECs highlighted the antiapoptotic and proangiogenic properties of adiponectin but could not demonstrate accelerated differentiation of endothelial cells into tube-like structures at elevated glucose levels.

Conclusions.

External administration of adiponectin at elevated glucose levels may not be useful in the treatment of diabetes mellitus-related vascular deficiency diseases.