Anti-diabetic drugs may also reduce blood vessel dysfunction associated with aging

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An FDA-approved drug to lower blood sugar in adults with type 2 diabetes may also reduce blood vessel dysfunction associated with aging, according to a new study from the University of Missouri School of Medicine.

The researchers first looked at the role that aging plays in the function and stiffness of human blood vessels. Next, they assessed how treatment with the sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin (Empa) improved blood vessel function and reduced arterial stiffness in aged male mice.

Cardiovascular disease is the leading cause of death among older adults in the United States. Weight loss, physical activity, antihypertensive treatment, and lipid-lowering drugs have shown variable effectiveness in improving blood vessel function and reducing arterial stiffness. But additional approaches are needed to improve vascular health in older adults.”


Camila Manrique-Acevedo, MD, Associate Professor of Medicine

The study first compared the function and stiffness of blood vessels in 18 healthy human patients -; average age of 25 -; with 18 patients with an average age of 61 years. They found that older patients had impaired endothelial function and increased aortic stiffness compared to younger patients.

“Our findings in young and older adults support previous clinical data demonstrating the impact of aging on blood vessel function and arterial stiffness,” Manrique-Acevedo said. “Most importantly, we were able to reproduce this data in a rodent model.

In order to study the effects of Empa on vascular aging, 72-week-old male mice were divided into two groups. Twenty-nine were fed an Empa-enriched diet for six weeks, while the other half received a standard diet. After analyzing both groups six weeks later, researchers found that Empa-treated mice showed improved blood vessel function, reduced arterial stiffness, and other vascular benefits.

“To our knowledge, this is the first study to examine the potential role of SGLT2 inhibition in reversing vascular aging,” Manrique-Acevedo said. “And our findings highlight the need for further clinical investigations to determine the potential role of SGLT2 inhibition as a therapeutic tool to delay or reverse vascular aging in humans.”

The entire MU research team consisted of Jaume Padilla, PhD, associate professor of nutrition and exercise physiology and co-corresponding author of this work; Luis Martinez-Lemus, DVM, PhD, professor of medical pharmacology and physiology, and R. Scott Rector, PhD, associate professor of nutrition. It also included postdoctoral fellows Rogerio Soares, PhD, Francisco Ramirez-Perez, PhD, Thaysa Ghiarone, PhD, and Francisco Cabral-Amador, PhD; research specialist Mariana Morales Quinones; assistant research professors Christopher Foote, PhD, and Neekun Sharma, PhD; and graduate students James A. Smith and Gavin Power.

Their study, “SGLT2 inhibition attenuates arterial dysfunction and decreases vascular F-actin content and expression of proteins associated with oxidative stress in aged mice,” was recently published in the journal GeroScience. Part of the support for this study was provided by the National Institutes of Health and a VA Merit Grant. The content does not necessarily represent the official views of the funding agency. The authors declare no potential conflict of interest.

Highlighting the promise of personalized healthcare and the impact of large-scale interdisciplinary collaboration, the NextGen Precision Health initiative brings together innovators from the University of Missouri and three other research universities in the UM system in the pursuit of life-changing advances in precision health. It’s a collaborative effort to leverage Mizzou’s research strengths toward a better future for the health of Missourians and beyond. The Roy Blunt NextGen Precision Health building at MU anchors the overall initiative and expands collaboration between researchers, clinicians and industry partners in the cutting-edge research center.

Source:

University of Missouri-Columbia

Journal reference:

Soares, Registered Nurse, et al. (2022) Inhibition of SGLT2 attenuates arterial dysfunction and decreases vascular F-actin content and expression of proteins associated with oxidative stress in aged mice. GeroScience. doi.org/10.1007/s11357-022-00563-x.

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