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Chestnut Studying 摘要 To determine whether hyperlipidemia and chronic kidney disease (CKD) have a synergy in accelerating vascular inflammation via trained immunity (TI), we performed aortic pathological analysis and RNA-sequencing of high-fat diet (HFD)-fed 5/6 nephrectomy CKD (HFD+CKD) mice. We made the following findings: 1) HFD+CKD increased aortic cytosolic lipopolysaccharide (LPS) levels, caspase-11 (CASP11) activation, and 998 gene expressions of TI pathways in the aorta (first-tier TI mechanism); 2) CASP11 —/— decreased aortic neointima hyperplasia, aortic recruitment of macrophages, and casp11-gasdermin D-mediated cytokine secretion; 3) CASP11—/— decreased N-terminal gasdermin D (N-GSDMD) membrane expression on aortic endothelial cells and aortic IL-1B levels; 4) LPS transfection into human aortic endothelial cells resulted in CASP4 (human)/CASP11 (mouse) activation and increased N-GSDMD membrane expression; 5) IL-1B served as the second-tier mechanism
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