New research at the Roy Blount NextGen Precision Health Building has uncovered a potential treatment for the underlying cause of cardiovascular disease in people with type 2 diabetes.
More than 30 million Americans have type 2 diabetes. One of the common characteristics of diabetes is damage to endothelial cells in the vasculature, causing blood vessels to stiffen and become inflexible. Over time, this can lead to the development and progression of cardiovascular disease, which is the leading cause of death in diabetic patients. As endothelial dysfunction is causally linked to cardiovascular disease, there is an increasing need to identify new therapeutic targets to improve endothelial function in patients with type 2 diabetes.
A research team from the University of Missouri found elevated neuraminidase activity in the circulation of mice and humans with type 2 diabetes. In a series of mechanistic experiments in cultured endothelial cells and isolated blood vessels, the team was able to link increased neuraminidase to endothelial dysfunction.
“We know that neuraminidase is elevated in the blood of people with type 2 diabetes and that it promotes endothelial dysfunction, so it is important to target this as a way to address the cardiovascular complications faced by people with type 2 diabetes,” he said. Luis Martinez Lemus, Veterinarian, PhDJames O. Davis, Distinguished Professor of Cardiovascular Research at the University of Missouri School of Medicine;
The team also found that inhibiting neuraminidase with zanamivir, an oral, inhaled drug used to treat influenza viruses, improved endothelial function in diabetic mice.
“This study elucidates the molecular mechanisms by which neuraminidase promotes endothelial dysfunction and may allow these mechanisms to be exploited therapeutically,” said Dr. Dr. Jaume Padilla“This research is very important because improving vascular function in people with type 2 diabetes could help them live longer, better lives,” said Dr.
“Neuraminidase inhibition improves endothelial function in diabetic mice” and “Neuraminidase-induced phosphatidylserine externalization activates ADAM17 and inhibits insulin signaling in endothelial cells” was recently published in the American Journal of Physiology – Cardiac and Circulatory Physiology. In addition to Martinez-Lemus and Padilla, the University of Missouri research team included: Camila Manrique Acevedo, MDDistinguished Professor of Diabetes and Director of Undergraduate Research in the School of Medicine; Larissa Ferreira-Santos, PhD, Thaysa Ghiarone, PhD, and Francisco Ramirez-Perez, PhD, postdoctoral researchers at NextGen Precision Health; Christopher Foote, PhD, assistant professor of medical pharmacology and physiology; and James Smith, Marc Augenreich, Neil McMillan, and Gavin Power, doctoral students in nutrition and exercise physiology. Andrew Wheeler, MDSurgeon General, University of Missouri Health Care Weight Management Center, Katherine Barr, Senior Research Specialist, School of Medicine, Anaya Arul, MD, Assistant Professor, School of Medicine, Dr. Shawn Benderassociate professor in the School of Veterinary Medicine, Dr. Mariana Morales Quinones, senior research specialists at NextGen Precision Health, Morgan Williams and Juan Gonzalez Vallejo, NextGen Precision Health.
