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. 2021 Nov 2;14:5699–5711. doi: 10.2147/JIR.S336964

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© 2021 Guo et al.

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NLRP3 inhibition effectively protected right ventricular function, relieved the asymmetrical IL-1β elevation and erased the change in inflammation in the right ventricle. (A) The FAC in PAH+LPS rats (SD rats were fed for 28 days after intraperitoneal injection of MCT; intravenous injection of saline was performed 1 hour before LPS injection, and the samples were collected 6 hours after intraperitoneal injection of LPS) and PAH+MCC950+LPS rats (SD rats were fed for 28 days after intraperitoneal injection of MCT; intravenous injection of MCC950 was performed 1 hour before LPS injection, and the samples were collected 6 hours after intraperitoneal injection of LPS) before and after LPS injection is shown. The significance of differences was determined with two-way ANOVA (n = 6). (B) IL-1β immunofluorescence in the right ventricle of PAH+LPS rats and PAH+MCC950+LPS rats 6 h after LPS injection. (C) Pretreatment with MCC950 significantly alleviated the asymmetrically increased IL-1β expression in myocardial tissue of the right ventricle. The ratio of the IL-1β area% in the right ventricle to that in the left ventricle is shown. The significance of differences was determined with unpaired Welch’s t-test (n = 3). (D) The IL-1β mRNA level in the right ventricles of rats in the two abovementioned groups. The significance of differences was determined with unpaired Welch’s t-test (n = 6). (E) The TNF-α mRNA level in the right ventricles of rats in the two abovementioned groups. The significance of differences was determined with unpaired Welch’s t-test (n = 6). (F) The IL-6 mRNA level in the right ventricle of rats in the two abovementioned groups. The significance of differences was determined with unpaired Welch’s t-test (n = 6). (G) A total of 67 cytokines and chemokines in right ventricular tissue were tested with a cytokine array. The heat map shows that the expression of 6 factors (MCP-1, b-NGF, CINC-1, CINC-2, CINC3, and fractalkine) was increased in the right ventricular myocardium of PAH rats after LPS injection. (H) Heat map showing that 13 factors (MCP-1, b-NGF, CINC-1, CINC-2, CINC3, ICAM-1, TIMP-1, LIX, IL-1β, IL-1α, L-selectin, TWEAK R, and P-cadherin) remained at low levels in the right ventricular myocardium of PAH+MCC950+LPS rats after LPS injection. The significance of differences between two groups was determined with an unpaired Student’s t-test (n = 3–4). *p < 0.05, ***p < 0.001, ****p < 0.0001.