The role of protein O-GlcNAcylation on primary aldosteronism

Abstract

Primary Aldosteronism (PA) is a pathological condition in which the adrenal glands increase the production of aldosterone. In the vasculature, the deleterious effects of high aldosterone concentrations comprise its pro-oxidant, pro-inflammatory, and pro-proliferative properties. The post-translational modification (PTM) O-GlcNAc changes the function, stability, and subcellular location of many proteins related to cardiovascular function and control. beta-catenin is a transcriptional factor that controls the proliferation and maintenance of cells in both embryogenesis and adulthood and emerged as a player in PA. In vascular smooth muscle cells (VSMCs), beta-catenin controls proliferation via expression of Cyclin D1 and p21. Of importance, evidence shows that beta-catenin has its activity regulated by O-GlcNAc. Considering that (i) Aldosterone levels negatively impact cardiac and vascular structure and function. (ii) beta-catenin plays a role in cellular growth and proliferation and (iii) O-GlcNAc is a very dynamic PTM linked to cardiovascular health and disease. This study will test the hypotheses that PA, increases O-GlcNAc levels and mediates aldosterone effects in blood vessels contributing to proliferation of VSMCs, through the modification of beta-catenin by O-GlcNAc. (AU)