Fig. 9: PCSK9 colocalized with CAP1 in atherosclerotic plaques, and PCSK9-induced phosphorylation was inhibited in CAP1-heterozygous knockout mice. | Nature Communications

Fig. 9: PCSK9 colocalized with CAP1 in atherosclerotic plaques, and PCSK9-induced phosphorylation was inhibited in CAP1-heterozygous knockout mice.

From: PCSK9 stimulates Syk, PKCδ, and NF-κB, leading to atherosclerosis progression independently of LDL receptor

Fig. 9

a Immunofluorescence staining for PCSK9 (red) and F4/80 (green) in arteries under D-flow in Cap1+/+ and Cap1+/− mice injected with AdV-CTRL or AdV-PCSK9. PCSK9 and F4/8 expression significantly increased in Cap1+/+ mice with AdV-PCSK9 compared with that in AdV-CTRL. However, in Cap1+/− mice, the increase in PCSK9 was less significant and F4/80 showed no significant change (N = 3). The scale bar represents 10 μm. b Partially ligated Cap1+/+ and Cap1+/− mice with only arteries exposed to D-flow were compared after AdV-CTRL or AdV-PCSK9 injection. Immunofluorescence staining of PCSK9 (red, upper panels; N = 3), p-Syk (gray, middle panels; N = 4), and p-PKCδ (green, bottom panels; N = 3). AdV-PCSK9 increased PCSK9 expression in Cap1+/+ mice, lesser than in Cap1+/− mice. Additionally, p-Syk and p-PKCδ increased more significantly in Cap1+/+ mice than in Cap1+/− mice. The scale bar represents 10 μm. c Immunofluorescence images of arteries under D-flow from Cap1+/+ mice injected with AdV-PCSK9 showing colocalization of PCSK9 (red), CAP1 (gray), and F4/80 (green). The scale bar represents 5 μm. d Immunofluorescence images of arteries under D-flow from Cap1+/+ mice injected with AdV-PCSK9 showing colocalization of PCSK9 (red), CAP1 (gray), and CD31 (green). The scale bar represents 5 μm. e Immunofluorescence images of arteries under D-flow from Cap1+/+ mice injected with AdV-PCSK9 showing colocalization of PCSK9 (red), CAP1 (gray), and αSMA (green). The scale bar represents 10 μm. f Immunofluorescence staining for PCSK9 (red), αSMA (green), and F4/80 (gray) in arteries under D-flow from Cap1+/+ mice injected with AdV-PCSK9. White arrow indicates PCSK9, αSMA, and F4/80 colocalization. The yellow arrow denotes PCSK9 and αSMA colocalization (top middle panel). The three bottom panels show the colocalization of PCSK9 and αSMA (bottom left), PCSK9 and F4/80 (bottom middle), and αSMA and F4/80 (bottom right), respectively. The scale bar represents 10 μm. g Schematic model showing PCSK9-mediated inflammation in monocytes mediated by CAP1 recruiting PKCδ and Syk and modulating PCSK9-mediated inflammatory signal transduction. Group differences were compared using the unpaired t-test (two-tailed). All data are presented as mean values ± SEM.

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