Abstract 1210: Interferon-gamma-induced CD40/CD40 Ligand Pathway Activation Mediates Atherosclerotic Plaque Progression and Destabilization in ApoE-Knockout Mice
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Background: A triggering role of interferon-gamma (IFN-g) is suggested in atherosclerotic plaque formation by activating inflammatory process. Soluble mutant of IFN-g receptor (sIFNgR) blocks IFN-g-induced activation of the target cells in vivo. The immune mediator CD40 ligand (CD40L) and its receptor CD40 are crucial for initiation of plaque formation and for progression and destabilization of advanced plaque by producing monocyte chemoattracting protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9). We assessed the hypothesis that postnatal inhibition of intrinsic IFN-g would reduce and stabilize advanced plaques via inhibition of the CD40L/CD40 pathway. Methods and Results: From 8-week old (w), apoE-knockout (apoEKO) mice were fed daily high-fat diet. At 12 w when aortic plaques had been established, mice were randomized to 2 groups: sIFNgR-treated mice received gene transfer of naked DNA plasmid encoding sIFNγR into the thigh muscle twice at 12 and 14 w. Mock-treated mice receiv
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Background: A triggering role of interferon-gamma (IFN-g) is suggested in atherosclerotic plaque formation by activating inflammatory process. Soluble mutant of IFN-g receptor (sIFNgR) blocks IFN-g-induced activation of the target cells in vivo. The immune mediator CD40 ligand (CD40L) and its receptor CD40 are crucial for initiation of plaque formation and for progression and destabilization of advanced plaque by producing monocyte chemoattracting protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9). We assessed the hypothesis that postnatal inhibition of intrinsic IFN-g would reduce and stabilize advanced plaques via inhibition of the CD40L/CD40 pathway. Methods and Results: From 8-week old (w), apoE-knockout (apoEKO) mice were fed daily high-fat diet. At 12 w when aortic plaques had been established, mice were randomized to 2 groups: sIFNgR-treated mice received gene transfer of naked DNA plasmid encoding sIFNγR into the thigh muscle twice at 12 and 14 w. Mock-treated mice receiv
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