Figure 2
Vascular miR-204 is upregulated by ER stress and promotes endothelial dysfunction. (A,B) Systemic infusion with miR-204 inhibitor reverses ER stress-induced endothelial dysfunction. Endothelium-dependent relaxation thoracic aortas (A) and mesenteric resistance arteries (MRA) (B) of C57/Bl6 mice infused with miR-204 I (0.2 mg/mouse/week) and treated with tunicamycin (0.75 mg/kg, 2 injections/week for two weeks). Control vessels were harvested from mice treated with Veh and infused with miR SC. n = 5. *p < 0.05 vs miR SC + Veh, miR-204 I + Veh, and miR-204 I + Tunica. ^p < 0.05 miR-204 I + Tunica vs miR SC + Veh. (C–G) Systemic infusion with miR-204 I reverses Tunica-induced vascular ER stress. MiR-204 expression quantified by qPCR in thoracic aortas (C) and MRAs (D) of mice infused with miR-204 I and treated with Tunica. Values are normalized to RNU6 and expressed relative to miR SC + Veh. Immunoblots for ER stress markers (E), in situ hybridization for miR-204 (F), and immunofluorescence and quantification for BIP (G) in MRAs of mice from A–D above. Data is representative of three independent experiments. Von Willebrand Factor (VWF) was used as endothelial marker. BIP expression shown relative to miR SC + Veh. *p < 0.05 vs miR SC + Veh, miR-204 I + Veh, and miR-204 I + Tunica. #p < 0.05 vs miR SC + Veh.
