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Scientists Found New Targets to Reduce Blood Vessel Damage

Scientists identified new targets that can reduce blood vessel damage in diabetes, according to a study published on July 9, 2018.

This study was conducted by the researchers at the Medical College of Georgia at Augusta University. In diabetes, the levels of enzyme known as PDIA1, which enables a healthy homeostasis of endothelial cells as well as production of new blood vessels decreases and the activity of Drp1, a key regulator of fission regulated by PDIA1 increase. Imbalance of these causes separation of endothelial cells and their powerhouses, thereby causing a vicious cycle where too much reactive oxygen species are produced by the mitochondria.

The discoveries help in providing new treatment targets for diseases associated with endothelial cell senescence or aging. Potential points of intervention include restoring a healthy balance of PDIA1 and Drp1 and/or reducing the high oxidative stress that throws off the balance in diabetes and other disease.

Specific amount of ROS is needed for various body functions, however, high levels are associated with aging throughout the body. Within the endothelial cells, the mitochondria primarily produce ROS as fuel and it in turn helps fuel mitochondria. Normal levels of ROS actually activates the PDIA1 enzyme and are a signaling molecule for angiogenesis, which is the formation of new blood vessels. On knocking out PDIA1 in endothelial cells that are isolated from human blood vessels, it was found that presence of protein necessary to maintain endothelial cell function. Moreover, there was less cell growth and proliferation as well as impaired angiogenesis and ability to dilate.

When researchers was studying about regulation of ROS levels by PDIA1 in endothelial cells, they found that the loss of PDIA1 induces both a slight increase inside the endothelial cells and mitochondrial dysfunction, including significantly increasing the amount of ROS produced by mitochondria. Scientists are further studying about delivery systems for PDIA1.