Microbiota composition modulates inflammation and neointimal hyperplasia after arterial angioplasty.

Autor:	Cason CA; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill., Kuntz TM; Department of Surgery, University of Chicago, Chicago, Ill., Chen EB; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill., Wun K; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill., Nooromid MJ; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill., Xiong L; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill., Gottel NR; Department of Surgery, University of Chicago, Chicago, Ill., Harris KG; Department of Medicine, University of Chicago, Chicago, Ill., Morton TC; Department of Ecology and Evolution, University of Chicago, Chicago, Ill., Avram MJ; Department of Anesthesiology, Mary Beth Donnelley Clinical Pharmacology Core Facility, Northwestern University Feinberg School of Medicine, Chicago, Ill., Chang EB; Department of Medicine, University of Chicago, Chicago, Ill., Gilbert JA; Department of Surgery, University of Chicago, Chicago, Ill., Ho KJ; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address: kho1@nm.org.
Jazyk:	angličtina
Zdroj:	Journal of vascular surgery [J Vasc Surg] 2020 Apr; Vol. 71 (4), pp. 1378-1389.e3. Date of Electronic Publication: 2020 Feb 05.
DOI:	10.1016/j.jvs.2019.06.208
Abstrakt:	Background: Neointimal hyperplasia is a major contributor to restenosis after arterial interventions, but the genetic and environmental mechanisms underlying the variable propensity for neointimal hyperplasia between individuals, including the role of commensal microbiota, are not well understood. We sought to characterize how shifting the microbiome using cage sharing and bedding mixing between rats with differing restenosis phenotypes after carotid artery balloon angioplasty could alter arterial remodeling. Methods: We co-housed and mixed bedding between genetically distinct rats (Lewis [LE] and Sprague-Dawley [SD]) that harbor different commensal microbes and that are known to have different neointimal hyperplasia responses to carotid artery balloon angioplasty. Sequencing of the 16S ribosomal RNA gene was used to monitor changes in the gut microbiome. Results: There were significant differences in neointimal hyperplasia between non-co-housed LE and SD rats 14 days after carotid artery angioplasty (mean intima + media [I + M] area, 0.117 ± 0.014 mm 2 LE vs 0.275 ± 0.021 mm 2 SD; P < .001) that were diminished by co-housing. Co-housing also altered local adventitial Ki67 immunoreactivity, local accumulation of leukocytes and macrophages (total and M2), and interleukin 17A concentration 3 days after surgery in each strain. Non-co-housed SD and LE rats had microbiomes distinguished by both weighted (P = .012) and unweighted (P < .001) UniFrac beta diversity distances, although without significant differences in alpha diversity. The difference in unweighted beta diversity between the fecal microbiota of SD and LE rats was significantly reduced by co-housing. Operational taxonomic units that significantly correlated with average I + M area include Parabacteroides distasonis, Desulfovibrio, Methanosphaera, Peptococcus, and Prevotella. Finally, serum concentrations of microbe-derived metabolites hydroxyanthranilic acid and kynurenine/tryptophan ratio were significantly associated with I + M area in both rat strains independent of co-housing. Conclusions: We describe a novel mechanism for how microbiome manipulations affect arterial remodeling and the inflammatory response after arterial injury. A greater understanding of the host inflammatory-microbe axis could uncover novel therapeutic targets for the prevention and treatment of restenosis. (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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