New research at the Roy Blunt NextGen Precision Health building has discovered a potential treatment for the root cause of cardiovascular disease in people with type 2 diabetes.

More than 30 million Americans live with type 2 diabetes. One of the common features of diabetes is stiffness and decreased flexibility of blood vessels caused by damage to the endothelial cells of the vasculature. Over time, this can lead to the development and progression of cardiovascular disease, which is the number one killer of people with diabetes. Because endothelial dysfunction is causally linked to cardiovascular disease, there is a considerable need to identify new therapeutic targets to improve endothelial function in patients with type 2 diabetes.

A team of researchers at the University of Missouri found that neuraminidase activity is elevated in the circulation of type 2 diabetic mice and humans. A series of mechanistic experiments using cultured endothelial cells and isolated blood vessels linked increased neuraminidase to endothelial dysfunction.

This is a means to address the cardiovascular complications faced by patients with type 2 diabetes, as patients with type 2 diabetes have increased levels of circulating neuraminidase, and its presence is known to promote endothelial dysfunction. It is important to target ”

Luis Martinez Lemus, DVM, PhD, James O. Davis Distinguished Professor of Cardiovascular Research, University of Missouri School of Medicine

The research team also found that neuraminidase inhibition using zanamivir, an orally 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 these mechanisms may have therapeutic potential,” said Jaume Padilla, Ph.D., associate professor of nutrition and exercise physiology at MU. “Improving vascular function in people with type 2 diabetes could help them live longer and better lives, which is why this study is so important.”

“Neuraminidase inhibition improves endothelial function in diabetic mice” and “Neuraminidase-induced phosphatidylserine externalization activates ADAM17 and impairs insulin signaling in endothelial cells” have recently been published. American Journal of Physiology – Cardiac and Circulatory Physiology. In addition to Martinez-Remus and Padilla, the MU research team includes Camila Manrique Acevedo, MD, distinguished professor of diabetes and director of faculty research in the School of Medicine; Dr. Larissa Ferreira-Santos, Dr. Thaysa Ghiarone, Dr. Francisco Ramirez-Perez, Postdoctoral Fellows at NextGen Precision Health; Dr. Christopher Foote, assistant professor of medical pharmacology and physiology; James Smith, Marc Augenreich, Neil McMillan, Gavin Power, Nutrition and Exercise Physiology PhD students. Dr. Andrew Wheeler, surgeon at MU Healthcare Weight Management Center; Katherine Barr, senior research specialist, School of Medicine; Anaya Arol, MD, assistant professor of medicine. Dr. Sean Bender, Associate Professor, College of Veterinary Medicine; Dr. Mariana Morales-Quinones, Senior Research Specialist at NextGen Precision Health. Morgan Williams and Juan Gonzalez Vallejo of NextGen Precision Health.