Manganese ion exhibits pro-angiogenic potential by reversing endotelial dysfunction induced by hyperglycemia

Abstract

Chronic hyperglycemia-induced endothelial dysfunction is a key factor in the vascular complications of diabetes. This study evaluated the pro-angiogenic potential of manganese ion (Mn²⁺) using human endothelial cells (HUVECs) cultured under hyperglycemic conditions (30 mmol/L D-glucose for 7 days). Proliferation, migration, tubulogenesis assays, and the expression of mitogenic and apoptotic markers were analyzed. The results showed that treatment with 100 µmol/L Mn²⁺ significantly enhanced cell proliferation and migration. Additionally, Mn²⁺ promoted tubule formation under hyperglycemia, increasing it by 300% compared to normoglycemia. Treatment also increased pERK levels, a mitogenic marker, while reducing Bax and cleaved caspase-3, both pro-apoptotic markers. In conclusion, Mn²⁺ exhibited clear potential to reverse endothelial dysfunction and promote angiogenesis under hyperglycemic conditions, suggesting its potential use in regenerative therapeutic strategies for vascular diseases associated with diabetes.