Vascular Complications of Diabetes: Due to One Missing Enzyme?

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Many tragic complications of diabetes, including amputations, heart attack, stroke, and blindness, are due to blood vessel damage. According to Xiaochao Wei, PhD, of the Washington University School of Medicine in St. Louis, all that vascular damage may be caused by a shortage of one enzyme: fatty acid synthase, or FAS.

To carry out the process of healing and forming new blood vessels, another critical enzyme, nitric oxide synthase (NOS), must be securely anchored to the blood vessel wall. That’s where FAS comes in. Dr. Wei discovered that FAS makes a molecule that attaches to NOS, allowing NOS to hook to the cell membrane and produce healthy blood vessels. People lacking insulin or with insulin resistance, however, have low levels of FAS.

Wei studied mice that had been genetically engineered to lack FAS in the endothelial cells that line their blood vessels. Mice with little or no FAS could not make the molecule that anchors NOS to the blood vessel cells. As a result, in the FAS-less mice, blood vessels were leaky and more vulnerable to the consequences of infection. Moreover, the mice couldn’t repair blood vessel damage or generate new blood vessel growth. When Wei looked at human endothelial cells, he saw a similar mechanism.

Because all the problems that the FAS-less mice experienced are also experienced by humans with diabetes, Wei hopes that using a drug or other enzyme to promote FAS activity in blood vessels might eventually solve some of the vascular problems experienced by diabetic patients. 

 

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