Figure 4

Conditional deletion of endothelial Sirt1 upregulates miR-204, promotes vascular ER stress and leads to endothelial dysfunction. Endothelial-dependent relaxation to acetylcholine (Ach) in thoracic aortas (A) and MRAs (D) of EC Sirt1^−/− and control Sirt1^flx/flx mice with and without Tunica treatment. n = 5. qPCR for miR-204 and TRPM3 in thoracic aortas (B,C) and MRAs (E,F) of EC Sirt1^−/− and Sirt1^flx/flx mice with and without treatment with Tunica. Values are normalized to RNU and expressed relative to Sirt1^flx/flx + Veh. n = 3. *p < 0.05 vs Sirt1^flx/flx + Tunica. #p < 0.05 vs EC Sirt1^−/− + Tunica. ^p < 0.05 vs EC Sirt1^−/− + Veh. In situ hybridization and quantification for miR-204 (G) and immunofluorescence with quantification for Sirt1 (H) and BIP (I) in MRAs of EC Sirt1^−/− and Sirt1^flx/flx mice with and without treatment with Tunica. Von Willebrand Factor (VWF) was used as endothelial marker. n = 3. Values expressed relative to Sirt1^flx/flx + Veh. *p < 0.05 vs Sirt1^flx/flx + Tunica. ^p < 0.05 vs EC Sirt1^−/− + Veh.