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UAB researchers discovered that the heart may retain a biological “memory” of past high blood sugar, increasing vulnerability to future cardiac stress even after glucose levels return to normal. The findings provide new insight into diabetes-related heart disease risk.
Samuel F. Chang, Ph.D., and Chae-Myeong Ha, Ph.D.A new study led by researchers at the University of Alabama at Birmingham Department of Pathology’s Division of Molecular and Cellular Pathology provides new insight into an occurrence known as metabolic memory, which may help explain why patients with diabetes remain at elevated risk for cardiovascular disease even after achieving glucose control.
Metabolic memory suggests that past elevated blood sugar levels may leave a lasting change in heart cells, but the biological mechanisms responsible for this effect are not fully understood.
First authors of the study, Samuel F. Chang, Ph.D., and Chae-Myeong “Jenna” Ha, Ph.D., examined whether a temporary increase in O-GlcNAcylation, a protein modification that occurs inside heart cells and is altered in diabetes, could create lasting effects on the heart. Although prior studies had suggested a link between glucose levels and these changes in susceptibility to disease, the UAB researchers from the laboratory of Adam R. Wende, Ph.D., hypothesized that a change specifically in O-GlcNAcylation was sufficient.
“We found that even after O-GlcNAc levels returned to normal, animal models 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,” said Wende, a professor in the Marnix E. Heersink School of Medicine.
The 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. O-GlcNAc memory is the idea that heart cells can retain a biological memory of prior metabolic stress, even after stress has been removed.
Adam Wende, Ph.D.The study also identified potential biological pathways involving fibrosis and oxidative stress that may contribute to these long-term effects.
“Although O-GlcNAc levels returned to normal, the heart remained altered in a way that made it more vulnerable to future stress,” Wende said. “When we later subjected the heart to pressure overload, those animals developed more severed hypertrophy, fibrosis and dysfunction than animal models without that prior exposure.”
These findings suggest that past metabolic conditions can leave a lasting impact on cardiac cells, even influencing how the cells respond to stress months later.
For patients living with diabetes, Wende says, the research reinforces the importance of early intervention.
“The most encouraging takeaway is that good glucose control matters, and it matters as early as possible,” Wende said. “These results highlight the importance of early intervention and consistent management of diabetes before long-lasting molecular changes become established.”
“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,” Wende said.
The paper, titled “Transient Increase in Cardiomyocyte Protein O-GlcNAcylation Enhances Susceptibility to Pressure Overload-Induced Cardiac Remodeling,” was published in the Journal of the American Heart Association.
Ultimately, Wende hopes treatments can be developed that control blood sugar and erase or prevent the harmful molecular memories that increase the risk of heart disease later in life.