Researcher’s study drills down into benefit of exercise

It’s axiomatic: Exercise is good for your health.

UNMC researcher Lie Gao, MD, PhD, is looking into one of the possible reasons why.

Dr. Gao, who has been at UNMC approximately 20 years, joined the UNMC Department of Anesthesiology earlier this year to extend his investigation of heart failure pathology into cardioprotection, a main benefit of physical activity.

“It has been incredibly exciting to have a talented scientist like Dr. Gao join the UNMC Department of Anesthesiology,” said Chair Steven Lisco, MD. “His line of inquiry has the potential to be groundbreaking. It is highly translatable and meshes perfectly with preclinical research currently being done in our department.”

Dr. Gao’s research, funded by a $2 million National Institutes of Health R01 grant, began in January and will run for the next four years.

Karsten Bartels, MD, vice chair of research, said: “This project has very high translational potential in at-risk perioperative patients, and we are excited that Dr. Gao chose our department to conduct his groundbreaking work.”

“It is well-known that regular exercise is fundamental for our health, particularly to the cardiovascular system,” Dr. Gao said. “The reasons, however, are still a mystery. My project is exploring its mechanism based on a new concept that all cells in our body can generate extracellular vesicles, a natural nanosized-vehicle capable of transporting substances from one part of the body to another.”

Dr. Gao said that researchers in the anesthesiology department have been at work in this fast-growing field for many years.

“Due to the high oxygen consumption and metabolic rate in exercise, contracting muscle produces a large amount of reactive oxygen species, a group of toxic molecules that may lead to potential damage to cellular proteins, lipids and DNA/RNA,” he said.

Fortunately, muscle is equipped with multiple potent protective mechanisms to neutralize these excessive toxic molecules.

“The first line of defense is led by a master transcription factor, termed Nrf2, which can help make more than 200 cytoprotective proteins and activate several key intracellular signaling pathways in muscle, according to our recent study in collaboration with Mass Spectrometry Core and Bioinformatics Core on the campus,” Dr. Gao said.

Investigators proposed that hundreds of these proteins function as an antioxidant cohort — not only protecting a muscle itself locally but also providing potential defense to other organs remotely, as the proteins can be transported by the extracellular vesicles from the contracting muscle to the heart during exercise. This helps protect against chronic heart failure and cardiac ischemia/reperfusion damage.

Dr. Gao’s theory caught the eye of Dr. Lisco, a longtime supporter of basic science research in his department, who brought Dr. Gao into anesthesiology so he could work alongside other researchers exploring similar investigative avenues.

“I was excited to join Dr. Lisco and his excellent team,” said Dr. Gao, adding that he had enjoyed 20 great years in the UNMC Department of Cellular and Integrative Physiology and will continue to collaborate with faculty members there.

“I expect to find some key molecules that mediate the exercise benefit,” he said. “These molecules will be therapeutic targets to treat oxidative stress-associated dysfunction — such as hypertension, heart failure and other key cardiovascular diseases.

“Although this is basic science research,” Dr. Gao said, “I expect to reveal information that can lead to translational efforts in patients, which is another great opportunity the new department can provide me.”

Dr. Bartels said that Dr. Gao is a welcome addition to the department for many reasons.

“In addition to his scientific prowess, Lie is a kind and generous mentor who has already started new collaborations within the department of anesthesiology,” Dr. Bartels said. “On behalf of the research team, we warmly welcome Dr. Gao’s arrival and pledge our support for his continued success.”