The disruption of macrophage HIF-1α alleviates BAPN-induced aortic dissection development.
(a) Representative pictures of aortas obtained from HIF-1αfl/fl and HIF-1α△lysm mice fed with BAPN (0.5%) for 28 days and aortic dissection incidence among HIF-1αfl/fl and HIF-1α△lysm mice fed with BAPN (n = 12).
(b) Survival rate of HIF-1αfl/fl and HIF-1α△lysm mice fed with BAPN (n = 12).
(c) Representative images of Verhoeff-Von Gieson staining of transverse cryosections of aortas from HIF-1αfl/fl and HIF-1α△lysm mice fed with BAPN and the quantification of elastin degradation (n = 6). Scale bar, 100 µm.
(d) Immunohistochemical staining for MMP2 (red, n = 3) and MMP9 (red, n = 3). Scale bar, 100 µm.
(e) qPCR analysis of Il-1β, Inos, Tnfα, Mif, Mcp-1, Icam1, and Vcam1 mRNA levels in aortas (n = 4).
(f) The concentration of various cytokines (IL-12, TNF-α, IFN-γ, MCP-1, IL-10, IL-6) in the plasma of BAPN-treated HIF-1αfl/fl and HIF-1α△lysm mice (n = 5).
(g) Systolic and diastolic blood pressure for 24 h in HIF-1αfl/fl and HIF-1α△lysm mice fed with BAPN for 28 days by telemetry measurements (n = 5).
(h) qPCR analysis of Tnfα, Il-1β, Il-6, and Inos mRNA levels in peritoneal macrophages from HIF-1αfl/fl and HIF-1α△lysm mice treated with 1.2 mM BAPN for 12 h (n = 5).
The data are presented as the mean ± SEM. For the nonparametric tests, the two-tailed Mann-Whitney U test was used for comparisons between two groups (c). Statistical significance is indicated by *P < 0.05, compared with HIF-1αfl/fl mice (c); Student's unpaired t-test was used for comparisons between two groups (e-h). Statistical significance is indicated by *P < 0.05, compared with HIF-1αfl/fl mice (e, f, h).