OxLDL-activated monocytes promote vascular smooth muscle cell phenotypic switch through NLRP3 inflammasome activation, likely contributing to atherosclerotic plaque instability.
Does monocyte-induced NLRP3 inflammasome activation promote vascular smooth muscle cell phenotypic switch in atherosclerosis?
Monocyte-induced NLRP3 inflammasome activation drives vascular smooth muscle cell phenotypic switching, highlighting a mechanism for atherosclerotic plaque destabilization.
(1) Background: Monocytes and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome orchestrate lipid-driven amplification of vascular inflammation promoting the disruption of the fibrous cap. The components of the NLRP3 inflammasome are expressed in macrophages and foam cells within human carotid atherosclerotic plaques and VSMCs in hypertension. Whether monocytes and NLRP3 inflammasome activation are direct triggers of VSMC phenotypic switch and plaque disruption need to be investigated. (2) Methods: The direct effect of oxLDL-activated monocytes in VSMCs co-cultured system was demonstrated via flow cytometry, qPCR, ELISA, caspase 1, and pyroptosis assay. Aortic roots of VSMCs lineage tracing mice fed normal or high cholesterol diet and human atherosclerotic plaques were used for immunofluorescence quantification of NLRP3 inflammasome activation/VSMCs phenotypic switch. (3) Results: OxLDL-activated monocytes reduced α-SMA, SM22α, Oct-4, and upregulation of KLF-4 and macrophage markers MAC2, F4/80 and CD68 expression as well as caspase 1 activation, IL-1β secretion, and pyroptosis in VSMCs. Increased caspase 1 and IL-1β in phenotypically modified VSMCs was detected in the aortic roots of VSMCs lineage tracing mice fed high cholesterol diet and in human atherosclerotic plaques from carotid artery disease patients who experienced a stroke. (4) Conclusions: Taken together, these results provide evidence that monocyte promote VSMC phenotypic switch through VSMC NLRP3 inflammasome activation with a likely detrimental role in atherosclerotic plaque stability in human atherosclerosis.
Burger et al. (Wed,) conducted a other in Atherosclerosis. OxLDL-activated monocytes and NLRP3 inflammasome activation was evaluated on VSMC phenotypic switch and NLRP3 inflammasome activation. OxLDL-activated monocytes promote vascular smooth muscle cell phenotypic switch through NLRP3 inflammasome activation, likely contributing to atherosclerotic plaque instability.
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