Medical College of Georgia scientists reported new functions of the copper transporter in the journal Nature Communications. The copper transporter ATP7A that moves copper across cellular membranes can serve as a target for treating cardiovascular diseases (CVD) like peripheral artery disease, myocardial infarction, and stroke.
Dr. Masuko Ushio-Fukai, vascular biologist, MCG's Vascular Biology Center (VBC), explained that the process of angiogenesis is mediated by the action of vascular endothelial growth factor (VEGFR2) on its receptor. Previous studies have noted a decline in ATP7A expression, loss of copper balance, and increased degradation of VEGFR2 in CVD like diabetes, said Dr. Tohru Fukai, vascular biologist and cardiologist, VBC. The new paper released by Dr. Ushio-Fukai and Dr. Fukai shows that VEGFR2 is stabilized and regulated by the binding of ATP7A to it.
Enzymes like superoxide dismutase and lysyl oxidase are provided with the copper needed for their activation by ATP7A through the Golgi network. The breakdown of reactive oxygen species is carried out by superoxide dismutase. New connective tissues for healthy skin, bones, and hair are synthesized by lysyl oxidase action.
Copper is an essential yet toxic micronutrient found in sesame seeds, cashews, walnuts, sweet potatoes, leafy greens like spinach and kale, soybeans, and shitake mushrooms. Other sources include oysters, tofu, lobster, and small clams. According to previous studies, this micronutrient stimulates the proliferation and migration of endothelial cells for angiogenesis. In animal models, tumor growth was observed to be reduced on a decline in copper. Similarly, in tissue forming new blood vessels, the levels of copper exhibited an increase. However, the exact mechanism of new blood vessel formation by stimulation from copper is not yet known.
VEGF and ATP7A
The study showed that the movement of ATP7A out of the Golgi apparatus is facilitated by VEGF. This ATP7A then binds and stabilizes the VEGF receptor. The VEGFR2 degradation is carried out by autosomes formed due to the loss of ATP7A in endothelial cells.
Ushio-Fukai said they would further study to identify drugs that would increase ATP7A levels. This ATP7A would further bind to the VEGF receptor and stabilize it.