Cardiovascular disease represents the leading cause of morbidity and mortality in individuals with obesity and/or diabetes. Although it is known that obesogenic and diabetogenic environments compromise vascular health, the underlying mechanisms remain to be fully elucidated. Post-translational modifications, such as methylation, are associated with histone-driven epigenetic regulation of gene expression. In addition, methylation of non-histone proteins is also emerging as a key regulator of a wide variety of cellular processes. Thus, changes in protein methylation, at both histone and non-histone levels, can be relevant for the impairment of the vasculature in metabolic disorders.

Our preliminary data from a unique animal model suggest that the modulation of the methylome in endothelial cells protects their function, regardless of their obesity and insulin resistance phenotype. In this project, we aim to fully characterize the mechanisms behind the preservation of endothelial function in these animals. The student will get a general knowledge of the basis of cardiovascular disease, epigenetics, and cellular and molecular biology. Moreover, the student will learn a number of techniques, including mouse aorta isolation, cell culture, RT-PCR, western blot, ELISA, imaging, overexpression/silencing, wire-myograph, and other functional studies. She/he will get a good insight into preclinical research and how to interpret data and communicate results.