Show-Me State Times

The human vascular system delivers oxygen, nutrients, hormones, and other vital substances to cells and organs in the body. When that system loses the ability to expand and contract—a process called arterial stiffening—the body becomes more susceptible to cardiovascular disease. In a notable discovery, a team of researchers at the University of Missouri has helped pioneer a molecular therapeutic that reduces arterial stiffness and improves blood vessel function, providing hope for those suffering from cardiovascular disease.

This team is determined to unveil new treatments for arterial stiffness—a key driver of cardiovascular disease (CVD)—while continually seeking ways to prevent it. They will investigate the inner workings of vascular dysfunction, particularly as it relates to older adults who suffer from this phenomenon more acutely.

This research is made possible by a $3 million grant over five years from the National Institutes of Health. The grant supports Camila Manrique-Acevedo, Luis Martinez-Lemus, and Jaume Padilla in their efforts to tackle one of the leading causes of mortality in America today.

“One of the strengths of our research program is our ability to test mechanistic and translational research questions using a plethora of approaches, including cell culture models, studies in isolated arteries and human clinical trials,” said Padilla, a professor of nutrition and exercise physiology in Mizzou’s College of Agriculture, Food and Natural Resources and the MU School of Medicine. “The process of translating findings from animal models to humans is made seamless in part because of the resources available at the NextGen Precision Health building.”

This team had one of the first established interdisciplinary labs in the NextGen Precision Health building, allowing them significant success in their advances for arterial stiffening treatments.

“Our research group studies the mechanisms of cardiovascular disease,” said Martinez-Lemus, a professor of medical pharmacology and physiology in the MU School of Medicine. “We know that conditions such as diabetes, hypertension and obesity, as well as factors such as age cause vasculature stiffening, and there have been no treatments to address that up to this point.”

Because arterial stiffening is associated with fatal conditions such as heart failure, chronic kidney disease and stroke, it’s important that researchers focus on understanding not only how and why it occurs but also how to treat it.

Thanks to the grant funding their work over five years researching mechanisms driving arterial stiffening in individuals 60 years or older—and determining efficacy therapeutics like sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin (Empa), which proved successful reducing stiffness improving vascular function other populations—team tests whether this inhibitor de-stiffens vascular smooth muscle cells thereby reducing arterial stiffening. They found SGLT2 inhibition could be potential treatment reduce progression cardiovascular disease older adults.

While Padilla notes there still no pharmacological treatment for vascular aging people can look after health vascular systems prioritizing few key lifestyle changes

“Because arterial stiffening can start as early adolescence it's vital people commit healthy lifestyle minimize risk cardiovascular disease” Padilla said “That means exercising regularly reducing sedentary time maintaining healthy body weight”

The development effective treatments complicated diseases years-long process begins idea evolves basic science experiments proceeds animal eventually human clinical trials

But because facilities NextGen Precision Health building team work each components simultaneously saves time expands avenues inquiry along way encourages collaboration researchers other specialties

"When NextGen building opened opportunity come together under one roof do basic science alongside human studies,” Padilla said. “We have Clinical Translational Science Unit wet lab third floor This positions us well forward reverse translational studies”

Manrique-Acevedo professor endocrinology clinician Mizzou's School Medicine echoed Padilla's sentiment adding NextGen's setup presents possibility collaborating fellow scientists

“Fighting cardiovascular disease common theme throughout building” Manrique-Acevedo said “For instance nowadays when people survive cancer they increased risk cardiovascular disease Women who experience reproductive complications increased risk cardiovascular disease That means our research closely impacts work colleagues second fourth floors house cancer reproductive neuroscience teams”

For Martinez-Lemus team's research pivotal illustrating fatal diseases such CVD don't appear overnight

“I think sometimes we are impressed devastation health news like cancer diagnosis” Martinez-Lemus said “But case cardiovascular disease factors lead often occur incrementally starting elevated blood pressure levels gradual arterial stiffening”

Highlighting promise personalized health care impact large-scale interdisciplinary collaboration University Missouri System’s NextGen Precision Health initiative bringing together innovators across system’s four research universities MU Health Care MU Extension industry partners pursuit life-changing precision health advancements dynamic effort leverage strengths entire UM System toward better future Missouri’s health initiative anchored Roy Blunt NextGen Precision Health building Columbia state-of-the-art research facility expanding collaborations between researchers clinicians industry leaders