title: Butyrate impairs atherogenesis by reducing plaque inflammation and vulnerability and decreasing NFκB activation.
abstract: OBJECTIVE
  Butyrate is a four-carbon fatty acid that presents anti-inflammatory, anti-oxidative and apoptotic properties in colon and several cell lines. Because atherosclerosis has important oxidative and inflammatory components, butyrate could reduce oxidation and inflammation, impairing atherogenesis. We evaluated the effects of butyrate supplementation of butyrate on atherosclerosis and its mechanisms of action.
  
  
  RESULTS
  ApoE knockout mice were fed on chow diet or 1% butyrate-supplemented chow diet (Butyrate) for 10 weeks to assess atherosclerosis lesions area and inflammatory status. Macrophage and endothelial cells were also pretreated with butyrate (0.5 mM) for 2 h before oxLDL stimulation to study oxLDL uptake and pro and anti-inflammatory cytokine production. Butyrate reduced atherosclerosis in the aorta by 50%. In the aortic valve, butyrate reduced CCL2, VCAM1 and MMP2 productions in the lesion site, resulting in a lower migration of macrophage and increased collagen depositions in the lesion and plaque stability. When EA.hy926 cells were pretreated with butyrate, oxLDL uptake, CD36, VCAM1, CCL2 TNF, IL1β and IL6 productions were reduced, whereas IL10 production was increased. These effects were accompanied by a lower activation of NFκB due to a lower nuclear translocation of the p65 subunit.
  
  
  CONCLUSIONS
  Oral butyrate is able to slow the progression of atherosclerosis by reducing adhesion and migration of macrophages and increasing plaque stability. These actions are linked to the reduction of CD36 in macrophages and endothelial cells, decreased pro-inflammatory cytokines and lower activation of NFκB all of these data support a possible role for butyrate as an atheroprotective agent.
authors.affiliation: Department of Biochemistry and Immunology of Universidade Federal de Minas Gerais, Brazil.
authors.forename: E C
authors.initials: EC
authors.lastname: Aguilar
authors.affiliation: Department of Biochemistry and Immunology of Universidade Federal de Minas Gerais, Brazil.
authors.forename: A J
authors.initials: AJ
authors.lastname: Leonel
authors.affiliation: Department of Biochemistry and Immunology of Universidade Federal de Minas Gerais, Brazil.
authors.forename: L G
authors.initials: LG
authors.lastname: Teixeira
authors.affiliation: Department of Physiology and Biophysics, of Universidade Federal de Minas Gerais, Brazil.
authors.forename: A R
authors.initials: AR
authors.lastname: Silva
authors.affiliation: Department of Pharmagology of Universidade Federal de Minas Gerais, Brazil.
authors.forename: J F
authors.initials: JF
authors.lastname: Silva
authors.affiliation: Department of Pharmagology of Universidade Federal de Minas Gerais, Brazil.
authors.forename: J M N
authors.initials: JM
authors.lastname: Pelaez
authors.affiliation: Department of Pharmagology of Universidade Federal de Minas Gerais, Brazil.
authors.forename: L S A
authors.initials: LS
authors.lastname: Capettini
authors.affiliation: Department of Pharmagology of Universidade Federal de Minas Gerais, Brazil.
authors.forename: V S
authors.initials: VS
authors.lastname: Lemos
authors.affiliation: Department of Physiology and Biophysics, of Universidade Federal de Minas Gerais, Brazil.
authors.forename: R A S
authors.initials: RA
authors.lastname: Santos
authors.affiliation: Department of Biochemistry and Immunology of Universidade Federal de Minas Gerais, Brazil. Electronic address: jalvarezleite@gmail.com.
authors.forename: J I
authors.initials: JI
authors.lastname: Alvarez-Leite
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001021:Aortic Valve / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000178:diet therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D020148:Butyric Acid / Q000378:metabolism / Q000627:therapeutic use*; D018955:CD36 Antigens / Q000037:antagonists & inhibitors / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D002467:Cell Nucleus; D002478:Cells, Cultured; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000209:etiology / Q000517:prevention & control*; D021381:Protein Transport; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D018955:CD36 Antigens; D051996:Transcription Factor RelA; D020148:Butyric Acid
keywords: Atherosclerosis; Butyrate; Fatty acid; Macrophage