Neurale upregulatie van SGLT2-MAP17-PDZK1-complex in nieren bij hartfalen

BACKGROUND:Congestive heart failure (CHF) is characterized by the activation of neurohumoral drive concomitant with avid fluid retention. Renal denervation alleviates this fluid retention. SGLT2 (sodium-glucose cotransporter 2) inhibitors have shown remarkable improvement in patients with cardiovascular diseases. We have recently demonstrated a relationship between enhanced renal sympathetic nerve activity and SGLT2 expression as well as function during CHF; however, the precise molecular mechanisms involved in the expression and translocation of SGLT2 and associated scaffolding proteins to the luminal membrane remain to be examined.METHODS:CHF was induced by coronary artery ligation followed by bilateral renal denervation 4 weeks later, in rats. Western blot analysis and immunohistochemistry were performed to evaluate changes in the expression of SGLT2, MAP17 (membrane-associated protein 17), PDZK1 (PDZ domain containing 1), and activation of ERK (extracellular signal-regulated kinase