Epigenetic mechanisms of hyperglycemic memory

Recently the concept emerged that prolonged exposure to altered metabolic conditions, including hyperglycemia, may epigenetically imprint human cells permitting vertical or horizontal transfer to "descendants". Although mechanistically ill understood, the hyperglycemic/epigenetic memory may represent one of the major limitations for the application of cell therapy to treatment of chronic heart disease where a relatively prolonged period of ex vivo cellular expansion is required. Hyperglycemic memory, in fact, seems to contribute to the establishment of an epigenetic "reminiscence" of the altered metabolic state, to which, cells from diseased bodies have been exposed. This review summarizes the most relevant concepts and observations about the mechanisms underlying the onset of stable information inside the epigenome leading to the development of a diseased phenotype. Special attention is given to epigenetic drugs and how they have been used in experimental, preclinical and clinical settings to treat dysmetabolism, diabetes and their complications.