Fig. 8

Effects of PCSK9 inhibition or statin administration on TGF-β1 overexpressing transgenic mice. (A) Experimental scheme of the TGF-β1 transgenic mouse study. Male and female transgene + mice and transgene − littermates aged 6–8 weeks were fed 0.5 mg/ml doxycycline in water ad libitum for 4 weeks, with intraperitoneal injection of alirocumab (10 mg/kg) weekly and oral administration of atorvastatin (10 mg/kg) five times per week. Quantitative RT-PCR measurement of NLRP3 (B), ASC (C), caspase-1 (D), and IL-1β (E) mRNA expression in the lungs is shown. (F) MT staining also showed inhibition of peribronchial and perivascular fibrosis by PCSK9 inhibition or statin administration in transgenic mice (original magnification: 100×). (G) Quantitative analyses of the fibrosis area were performed using an image analysis system. Quantification of EMT markers in the lungs was performed using mRNA expression of collagen 1 (H), collagen 3 (I), and fibronectin (J). The results are expressed as the mean ± SEM (n = 6 per group). Statistical analysis was performed using one-way ANOVA with Bonferroni correction. *: P < 0.05, **: P < 0.01, and ***: P < 0.001. DC: doxycycline; WT: wild-type