Diabetes Mellitus Aggravates Hemorrhagic Transformation after Ischemic Stroke via Mitochondrial Defects Leading to Endothelial Apoptosis
Figure 6
Diagram illustrating the postulated mechanism through which hyperglycemia aggravates hemorrhagic transformation after ischemic stroke.
Hyperglycemia increases the activity of MMP-9 in an ROS-independent manner, which promotes the opening of mitochondrial permeability transition pores (mitochondrial depolarization; Δψm ↓↓). The mitochondria that have lost normal function can no longer produce ATP, and emit various pro-apoptotic factors, such as AIF and cytochrome c into the cytosol. These factors subsequently activate caspase-3 and induce apoptotic cell death in HBMVECs. On the other hand, functional failure leads to morphological alteration of mitochondria, (fragmentation, vacuolation, cristae disruption). Eventually, both of these functional and morphological disturbances result in the aggravation of hemorrhagic transformation after ischemic stroke.