Iron exposure reduces viability and plasticity of brain microvascular endothelial cells after hypoxic injury (670.2)

Abstract

Diabetes increases the risk, causes bleeding into the brain, and worsens functional outcomes after ischemic stroke. We have previously shown that diabetic Goto‐Kakizaki (GK) rats have increased yet dysfunctional angiogenesis, profuse bleeding into the brain and poor vascular repair if subjected to stroke. The effect of bleeding on endothelial cell survival and repair is unknown. Here, we test the hypothesis that iron exposure reduces brain microvascular endothelial cell (BMVEC) viability and plasticity after ischemia/reperfusion in diabetes. To test this hypothesis, BMVECs isolated from Wistar (non‐diabetic) and GK rats were treated with 0.1 mM iron (III) sulfate, incubated 6 hours in hypoxia, and reoxygenated overnight. The cells were subjected to cell proliferation, migration and tube formation assays. GK BMVECs showed increased cell proliferation, migration and tube length under normoxia. Hypoxia reduced all three measures of angiogenesis for GK BMVECs. In addition, iron treatment further reduced migration and tube length of GK BMVECs exposed to hypoxia while it did not have an effect on control cells. These results suggest that iron has a deleterious effect on survival and angiogenic properties of GK BMVECs. More work is needed to investigate the exact mechanism of iron‐induced impairments but our work identifies iron chelation as a possible novel therapy to improve recovery after ischemic stroke.