Heart diseases are still the number one cause of death worldwide. According to the World Health Organization, cardiovascular diseases led to the deaths of about 9.8 million people in 2022 alone, accounting for about 32% of all deaths; 85% of these fatalities were due to heart attack or stroke. Scientists have now created a method to improve treatments for age-related heart disease. Reporting in Nature Communications, researchers showed heart health improved when the levels of brown fat or another fat molecule called lipokine 12,13-diHOME were increased.
Mammals, including humans carry white fat and brown fat. The primary type of fat in humans is white fat, which can store energy and release hormones. The accumulation of white fat is obesity. Brown fat is different, and can break down sugar and lipids to generate heat. Brown fat could potentially be utilized as an obesity treatment.
Previous work by this group has shown that exercising leads to increases in 12,13-diHOME, promoting good heart health. In this study, the researchers assessed blood samples obtained from volunteers of various ages, and determined that the levels of the lipokine 12,13-diHOME get lower as people age.
The investigators used a mouse model to transplant the brown fat of young mice into older mice. This process improved heart function in the older mice.
“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,” explained corresponding study author Kristin Stanford, PhD, professor at The Ohio State University College of Medicine, among other appointments.
The researchers wanted to raise these lipokine levels, and developed a gene therapy for that purpose. Since gene therapies have to work on DNA, they have to enter cells. Usually scientists use a harmless virus for this purpose. But the scientists used a non-viral method called Tissue Nanotransfection (TNT) instead to deliver the gene theraoy to raise lipokine levels in older male and female mice. This method was developed by study co-author Professor Daniel Gallego-Perez.
“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 penultimate author Professor Gallego-Perez, PhD, a chair at The Ohio State University, among other appointments.
This effort also showed that the 12,13-diHOME lipokine can directly inhibit the CaMKII protein, which helps regulate calcium levels in heart cells. This could explain the beneficial impact of 12,13-diHOME.
“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.
Sources: Ohio State University, Nature Communications