A 2024 human cell study investigated endothelial cell memories of hyperglycemia:

“Transient exposure to high glucose induces enduring transcriptional and chromatin alterations in endothelial cells (ECs). Activation of the NRF2 pathway with sulforaphane can mitigate these cellular memories, offering valuable insight into mechanisms and management of diabetes-associated complications.

Remarkably, sulforaphane not only prevents most of the aforementioned alterations caused by high glucose (HG), but it can also revert them once established. Although NRF2-independent chemoprotective mechanisms for sulforaphane have been described, our data showing that NRF2 gene overexpression resulted in a similar outcome suggest that beneficial effects conferred by sulforaphane in our HG and memory treatments occur mainly through activation of the NRF2 pathway.

We hypothesize that transient hyperglycemia impacts the epigenetic and functional states of enhancers, priming them to amplify or sustain the transcriptional changes. This mechanism mirrors how inflammation can imprint an enhancer’s epigenetic memory in immune cells and ECs. Ergo, in diabetes patients, repetitive cycles of pathological hyperglycemia could set enhancers into a pathological memory state.

The metabolic memory phenomenon has been studied for over three decades, yet currently, there are no specific treatments to ameliorate diabetes-associated vascular complications, which comprise the leading causes of morbidity and mortality in patients with this disease. Our study highlights the potential use of sulforaphane to revert high-glucose–induced transcriptional and epigenetic memories in human ECs.”

https://www.life-science-alliance.org/content/7/8/e202302382 “Reversal of high-glucose–induced transcriptional and epigenetic memories through NRF2 pathway activation”

A seven-month-long back-and-forth official correspondence history among these researchers and peer reviewers was also published in the Reviewer Comments pdf file, which was informative as to what was and wasn’t included in this study. For examples, in response to peer review comments, the researchers performed an unplanned in vivo rodent study that wasn’t added because it didn’t continue long enough to confirm in vitro human cell primary results. A five-item limitation section was added to this study, though.