ApoA1/HDL and sepsis-associated vascular endothelial injury: a narrative review

Figures

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  Fig. 1. Mechanism by which ApoA1 Inhibits Vascular Endothelial Inflammation. Lipid-free ApoA1 protein or its mimetic peptides interact with the ABCA1 receptor (a 12-transmembrane protein located in non-raft membrane domains, which has poor cholesterol) on macrophages. Concurrently, ApoA1 within (r)HDL interacts with the scavenger receptor SR-B1 (located in cholesterol-rich lipid raft domains). Both interactions promote the efflux of free cholesterol from macrophages to ApoA1 (indicated by a yellow straight arrow). Notably, the cholesterol efflux regulatory protein AIBP (ApoA1-Binding Protein) enhances the binding of ApoA1 to the ABCA1 receptor. Pathway ①: Inhibition of TLR4 consequently suppresses its downstream pro-inflammatory signaling pathways. Pathways ② and ③: Signaling pathways that inhibit inflammation, initiated respectively by the binding of ApoA1 to the ABCA1 receptor and HDL to the SR-B1 receptor. Pathway ④: Reconstituted HDL (rHDL) inhibits LPS-stimulated activation of the NLRP3 inflammasome. Created with BioGDP.com [167]

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  Fig. 2. ApoA1 maintains endothelial barrier integrity. Pathway ①: ApoA1 and ApoA1 mimetic peptides (such as D-4 F) inhibit EndMT in endothelial cells. Pathway ②: (r)HDL binds to the SR-B1 receptor, initiating signaling pathways that upregulate ANGPTL4 levels, thereby protecting the endothelial glycocalyx. Created with BioGDP.com [167]

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  Fig. 3. ApoA1 prevents vascular occlusion, thrombosis, and maintains vascular tone. Pathway ①: (r)HDL binds to the PDZK1 domain of SR-B1, leading to eNOS phosphorylation, producing NO to prevent microvascular occlusion and reducing vWF. Pathway ②: Lipid-free ApoA1 or (r)HDL binds to Ecto-F1-ATPase, activating the PI3Kβ/AKT signaling pathway. Pathway ③ and ④ upregulate COX-2 and PGI-2. Created with BioGDP.com [167]