Fig. 5

Disruption of CD146-HIF-1α in SMCs attenuates hypoxic PH. a Schematic of hypoxia-induced PH. b Left, WB analysis of CD146, HIF-1α and p-p65 in PASMCs from CD146^SMC-KO and CD146^WT mice. Right, relative expression of CD146, HIF-1α and p-p65 (n = 3 biological replicates for each group). c The mRNA levels of Ca9 and Pai1 in PASMCs were measured by real-time RT-PCR (n = 5 biological replicates for each group). d–h RVSP d, TPVRI e, SAP f, RV/(LV + S) g and body weight h in mice after 4 weeks of hypoxia (n = 10 mice per group). i Echocardiographic (PAAT, RVID, RVWT, and TAPSE) measurements and images. VTI, velocity time integral. j Echocardiography measurements were performed on CD146^SMC-KO and CD146^WT mice after exposure to hypoxic conditions for 4 weeks to determine PAAT, RVID, RVWT, TAPSE, CO, and CI (n = 10 mice per group). k Representative images of H&E and immunofluorescent staining of PAs (20–50 μm or 51–100 μm in diameter) stained with αSMA (green). Scale bar, 50 μm. l Quantification of vascular medial thickness for images in k (n = 5 mice per group, five PAs per mouse). m Quantification of PAs with > 50% luminal stenosis (n = 5 mice per group, five PAs per mouse). n Proportion of non-, partially-, or fully- muscularized pulmonary arterioles (20–50 μm in diameter) from hypoxia-treated mice (n = 8 mice per group). o Left, immunofluorescence staining of lung samples for αSMA (red) and PCNA (green). Right, quantification of the relative number of PCNA⁺/αSMA⁺ cells. p Left, TUNEL staining (green) with DAPI nuclear staining (blue) in small PAs. Right, quantification of the number of TUNEL⁺ cells. n = 4 o, p mice per group, three PAs per mouse. Scale bar, 50 μm. In all statistical plots, the results are expressed as mean ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001. n.s., not significant; by one-way ANOVA with Bonferroni post hoc analysis d–h, j or two-tailed Student’s t test b, c, l–p. All WB represent data from three b independent experiments. Source data are provided as a Source Data file