Patients with diabetes remain at higher risk for heart disease even after their blood sugar, or A1C level, is brought under control. The long-lasting effect, known as metabolic memory, suggests that past elevated A1C may leave lasting changes in heart cells. However, the biological mechanisms responsible for this impact are not fully understood.
Researchers from the laboratory of Adam R. Wende, Ph.D., a professor in the Division of Molecular and
Dr. Adam R. Wende Cellular Pathology, investigated this mechanism in a recently published paper, titled, “Transient Increase in Cardiomyocyte Protein O-GlcNAcylation Enhances Susceptibility to Pressure Overload-Induced Cardiac Remodeling” in the Journal of the American Heart Association.
First authors on the study Samuel F. Chang, Ph.D., and Chae-Myeong “Jenna” Ha, Ph.D., examined whether a temporary increase in O-GlcNAcylation, a modification that occurs on proteins inside heart cells and is altered in diabetes, could create a lasting effect on the heart.
Dr. Samuel F. Chang“We found that even after O-GlcNAc levels returned to normal, mice that had previously experienced elevated levels developed more severe heart enlargement and scarring when their hearts had also been subjected to high-blood pressure stress,” Wende said.
These findings provide evidence for an “O-GlcNAc memory” that may help explain how earlier metabolic changes can influence heart disease long after the original abnormality has resolved.
Dr. Jenna Ha The study also identified potential biological pathways involving fibrosis and oxidative stress that may contribute to this effect.
“Overall, this work adds an important potential mechanism to the field’s understanding of metabolic memory in diabetes and heart failure and may help guide future research into ways of preventing the long-term cardiac consequences of earlier metabolic stress.”
The researchers plan to submit applications for further funding from the NIH to explore the epigenetic and oxidative stress mechanisms in this study's findings.