New target emerging for treating diabetes-related blood vessel damage
A key enzyme that helps our proteins fold and function properly may also be a good therapeutic target to improve blood vessel health in diseases like diabetes and atherosclerosis, scientists say.
The enzyme is protein disulfide isomerase, or PDI, and scientists have increasing evidence that PDI is essential to the healthy remodeling of the endothelial cells that line our blood vessels and to the production of new blood vessels when we need them. This natural process is called angiogenesis, and it is impaired in diabetes.
"If we know the key mediator causing this, maybe we can target the molecule and treat the problem," says Dr. Masuko Ushio-Fukai, vascular biologist in the Vascular Biology Center at the Medical College of Georgia at Augusta University.
Ushio-Fukai is principal investigator on a new $1.4 million grant from the National Institutes of Health to further nail down the target and move toward "therapeutic" angiogenesis.
Her starting point is ROS, or reactive oxygen species. Many of us have heard about ROS, mostly that this natural byproduct of oxygen use is bad for us. But at normal levels, ROS has normal functions, which include working as a signaling molecule to promote angiogenesis. Under the stress of diabetes, endothelial cells produce too much ROS so angiogenesis doesn't work to repair the vasculature.
That's where PDI one comes in. Ushio-Fukai's team has shown that while normal levels of ROS activate PDI, high levels found in diabetes inactivate it.
The research team has evidence of ROS' relationship with one of PDI's major forms, PDIA1, in both normal and Continue reading