COLUMBUS, Ohio – Researchers at The Ohio State University Wexner Medical Center are using novel non-viral gene therapy technology to gain insight into how to treat age-related heart disease. Researchers found that adding more brown fat or increasing the level of a fat molecule, or lipokine, released by energy-burning brown fat helps preserve heart health.
"One of the biggest things we see with aging is cardiovascular disease, which increases dramatically in patients who are over 65. Now we're correlating it to a decrease in the lipokine 12,13-diHOME, and we're showing directly that when we increase this lipokine that we can essentially rescue cardiac function," said Kristin Stanford, PhD, professor in the Department of Surgery at The Ohio State University College of Medicine and associate director of the Dorothy M. Davis Heart and Lung Research Institute.
Results of the research, a collaboration between Ohio State's Colleges of Medicine and Engineering, were published recently in the journal Nature Communications.Brown fat is one of two types of fat in humans and other mammals. Sometimes called "good" fat, it differs from ordinary white fat in that it burns energy and generates heat via a process called thermogenesis.
In the study, researchers analyzed blood samples from young and older humans as well as mice and found 12,13-diHOME levels decrease with age for both males and females. They discovered transplanting brown fat from young mice into older ones improved cardiovascular function. Previous Ohio State research showed that exercising increased the levels of 12,13-diHOME, helping protect the heart.
Looking for a way to stimulate the release of the lipokine without exercise, scientists used non-viral gene therapy Tissue Nanotransfection (TNT) to increase it in older male and female mice.
"In just six weeks, we were able to really negate a lot of the effects of cardiovascular aging by using TNT to increase 12,13-diHOME. The results were quite striking with improvements to ejection fraction and the heart's pumping cycles," said Daniel Gallego-Perez, PhD, professor and Edgar C. Hendrickson Chair in Biomedical Engineering at The Ohio State University. Gallego-Perez, director of Advanced Nanotherapeutics at the Gene Therapy Institute, is lead inventor of TNT, a patented technology developed at Ohio State.
Researchers also discovered that 12,13-diHOME can directly block a protein called CaMKII, which is important for controlling calcium in heart cells. This helps explain how 12,13-diHOME might help keep the heart working well as it ages.
"Older adults are the fastest-growing demographic in the world and at the greatest risk of developing heart disease, the leading cause of death worldwide. More than 20% of the U.S. is projected to be over the age of 65 by the year 2030 so new technologies like what we're looking into are vital for combatting heart disease later in life," Stanford said.
The National Institute on Aging and National Institute of Diabetes and Digestive and Kidney Diseases supported the research. Both Standford and Gallego-Perez have patents pending related to the lipokine research.
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