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. Author manuscript; available in PMC: 2013 Jul 1.
Published in final edited form as: Nat Med. 2012 Dec 23;19(1):74–82. doi: 10.1038/nm.3040

Figure 6. MiR-424 and miR-503 can ameliorate the experimental pulmonary hypertension models in rodents.

Figure 6

(a) Expression levels of rno-miR-322 (hsa-miR-424 equivalent in rat) and miR-503 in rat lungs and isolated LECs 3 weeks after MCT injection and 4 weeks after SuHx. Expression levels of Apln mRNA in the rat LECs from two pulmonary hypertension models. *P < 0.01. (b) Expression of FGF2 and FGFR1 in the MCT and SuHx induced pulmonary hypertension rat lungs. (c) Right ventricular systolic pressure (RVSP) measurements in rats receiving intranasal delivery of lentiviral miR-424 and miR-503 (424/503-GFP) compared to control lentivirus (GFP) in the MCT prevention and rescue models, and the SuHx rescue model. *P < 0.001 for each model. (d) Microvascular muscularization analysis of lungs from rats receiving either intranasal GFP or 424/503-GFP in the three models. Smooth muscle actin is shown in red, vWF is shown in green. *P < 0.01 and **P < 0.001. (e) Assessment of PCNA expression in the lungs of the three pulmonary hypertension models receiving either GFP control or 424/503-GFP. PCNA is shown in red, vWF is shown in green. Orange bars denote the experimental pulmonary hypertension groups. *P < 0.001 and **P < 0.01. (f) H&E staining of the lungs from rats subjected to SuHx pulmonary hypertension induction receiving either GFP or 424/503-GFP. The average number of obliterated vessels per microscopic field is shown. Orange bars denote the experimental pulmonary hypertension groups. *P < 0.001, **P < 0.02. (g) FGF2 and FGFR1 protein levels in the lung homogenates of rats in the three models with either GFP or 424/503-GFP. FGF2 and FGFR1 expression in the isolated LECs from the MCT-Rescue and SuHx-Rescue models with GFP or 424/503-GFP. Orange bars denote the experimental pulmonary hypertension groups. *P < 0.05. (h) Proposed mechanism of endothelial signal linking APLN, miR-424/miR-503, and FGF2-FGFR1 in normal and PAH pulmonary endothelium.