Effect of α1-AT on VEGF and MMP-2 in HUVECs exposed to high glucose and hypoxia: a possible therapeutic approach towards diabetic retinopathy
Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus caused by hyperglycemia. Due to sustained hyperglycemia, the endothelial cells are damaged, leading to its dysfunction, which results in hypoxia. The hypoxic condition upregulates vascular endothelial growth factor (VEGF) activity that induces matrix metalloproteases (MMPs) to cause extracellular matrix degradation resulting in angiogenesis. Alpha-1 antitrypsin (α1-AT), an anti-protease, is known to downregulate MMPs. The objective is to assess the effect of α1-AT on VEGF and MMP-2 levels in an in vitro culture setup with various glucose concentrations and hypoxic conditions. Human Umbilical Vein Endothelial Cells (HUVECs) were cultured with different concentrations of glucose and cobalt chloride to induce high glucose and hypoxic conditions, respectively. Later, the cells were treated with α1-AT to assess its effect on VEGF and MMP-2. The VEGF and MMP-2 levels were evaluated in conditioned media by Enzyme-Linked Immunosorbent Assay. VEGF and MMP-2 levels were observed to be increased in the conditioned media of those cultured with high glucose concentrations and CoCl2. In contrast, the levels of VEGF and MMP-2 were observed to be reduce upon treatment with α1-AT. In conclusion, α1-AT reduced the levels of VEGF and MMP-2 in cells treated with high glucose concentration and hypoxia. This suggests the beneficial effect of α1-AT and its approach as a possible therapeutic target towards DR.