Fig 2: HDAC1 prevents atherosclerosis in mice via promoting IKBα expression(A) HDAC1 and IKBα levels in mice aorta tissues. (B) The area of aortic impairment (×400). (C) VCAM-1, ICAM-1, and MCP-1 levels in aorta tissues. (D) Serum TNF-α, IL-1, and IL-6 expression in mice; ∗p < 0.05. Measured data are described as mean ± standard deviation. Unpaired t test was used to analyze data between two groups; n = 10.

Fig 3: miR-40 inhibition suppresses the initiation of atherosclerosis in mice(A) Detection of miR-410 expression level in aorta tissues. (B) Arterial impairment and inflammation. (C) The area of aorta impairment. (D) Serum TNF-α, IL-1, and IL-6 levels in mice. (E) VCAM-1, ICAM-1, and MCP-1 expression in aorta tissues; ∗p < 0.05. Measured data are described as mean ± standard deviation, analyzed using independent samples t test between two groups; n = 10.

Fig 4: Effects of edoxaban on inflammatory factors and chemokines in the sera of mice with atrial fibrillation and vein thrombus. Plasma levels of (A) IL-1, (B) IL-4, (C) IL-8 and (D) TNF-α, (E) PGI2, (F) PGE2, (G) PGD2 and (H) PGF2α in mice with fibrillation and vein thrombus treated with edoxaban or phosphate-buffered saline. Data are presented as the mean ± standard deviation of the mean. **P<0.01 as indicated. IL, interleukin; TNF, tumor necrosis factor; PG, prostaglandin.

Fig 5: Hmgb2 mediates microglia pro-inflammatory response in stroke. (A) representative images show the expression of Hmgb2-SI (red, SI-tdT) and Hmgb2-I (red, I-tdT) in the cortex at 18 days after the injection of the AAV-PHP.eB-Hmgb2-SI/tdT or the AAV-PHP.eB-DIO-Hmgb2-I/tdT virus particles into the tail vein of the Cx3cr1-Cre mice. The sections are stained with anti-Iba1 (green). (B) the numbers and the soma size of the Iba1-labeted cells in the indivudal mice (circles) and their averages per group (triangles)at 18 days after the injection of AAV are plotted (ns = no significantly differences). (C) Hmgb2-I inhibits the Hmgb2 expression in microglia. The microglia lysates are prepared from mice expressing Hmgb2-SI or Hmgb2-I at 1, 2, or 3 days after operation with sham or stroke and blotted with anti-Hmgb2 or anti-α-tubulin, as indicated. (D) Relative expression (R.E) levels (defined by normalizing the band intensities of anti-Hmgb2 blots to the respective α-tubulin) in the individual mice (circles) and their averages per group (triangles) are plotted. Data are mean ± SEM (n = 5 mice per group, ns = no significantly differences, *p = 0.040; **p = 0.003; ***p < 0.0001 between Hmgb2-SI and Hmgb2-I, t-tests). (E) AAV-PHP.eB -DIO-Hmgb2-SI/tdT virus (green symbols) or AAV-PHP.eB -DIO-Hmgb2-I/tdT (blue symbols) virus particles or saline (pink symbols) were injected into the tail vein of the Cx3cr1-Cre mice. 18 days after the injection, mice were operated with sham or stroke. 24 or 72 hours after the operation, the ratios of IL-1, Cscl-16, Ctss, IL-6 and TNF-a in the extracellular space of stroke mice versus sham mice (stroke/Sham) are analyzed and plotted by the individual mice (circles) and their averages per group (triangles). Data are mean ± SEM (n = 5 mice per group, **p = 0.0041, ***p < 0.0001 between Hmgb2-SI and Hmgb2-I, t-tests). (F) the ratios of IL-10 in the extracellular space of stroke mice versus sham mice (stroke/Sham) are analyzed and plotted by the individual mice (circles) and their averages per group (triangles). Data are mean ± SEM (n = 5 mice per group, F (3,16) = 9.506, ns = no significantly differences, **p = 0.0038, 0.0011, 0.0054, BF ANOVA).