title: Relationship between regulatory T cells subsets and lipid profile in dyslipidemic patients: a longitudinal study during atorvastatin treatment.
abstract: BACKGROUND
  The CD4+ T-lymphocytes and their subtype CD4 + CD25(high)FoxP3+ regulatory T cells are receiving growing interest as major regulators of atherogenesis. We sought to investigate 1) whether the CD4 + cell subsets were expressed differently in dyslipidemic patients (Pts) and healthy subjects (HS) and 2) whether atorvastatin treatment could be associated in-vivo and in-vitro with cell changes in expression and functional response.
  
  
  METHODS
  CD4+ subsets frequency (CD4 + CD25(high)FoxP3+, CD4 + CD25-FoxP3+) and mRNA expression for FoxP3, IL-10 and TGF-β were evaluated in 30 consecutive Pts at baseline and after a 3-month atorvastatin therapy, and in 17 HS.
  
  
  RESULTS
  The % of CD4 + cells did not differ between HS and Pts. The % of CD4 + CD25(high)FoxP3+ was higher in Pts than HS and did not change during treatment. The CD4 + CD25-FoxP3+ cells were similar between the two groups and were lower in Pts at visit 2. Cytokine expression and FoxP3 did not differ in HS and Pts and no substantial change was observed during treatment. At visit 1, CD4 + CD25(high)FoxP3+ cells were significantly correlated with both total-cholesterol (r = 0.570, P = 0.0002), LDL-cholesterol (r = 0.715, P = 0.0001), Apolipoprotein B (r = 0.590, P = 0.0001). In-vitro atorvastatin (up to 5 μM) failed to induce any significant modulation of cell functions.
  
  
  CONCLUSIONS
  CD4 + CD25(high)FoxP3+ regulatory cells seem to be over-stimulated in the early pre-clinical phase of atherosclerosis and a relationship exists between their frequency and circulating lipids. A potential immuno-modulation by statin treatment is not achieved through a normalization in peripheral CD4 + cell subsets.
authors.affiliation: Research Center on Dyslipidemia, University of Insubria, Varese, Italy. luigina.guasti@uninsubria.it.
authors.forename: Luigina
authors.initials: L
authors.lastname: Guasti
authors.affiliation: Research Center on Dyslipidemia, University of Insubria, Varese, Italy. andrea.maresca@uninsubria.it.|Department of Clinical and Experimental Medicine, University of Insubria, Viale Borri 57, Varese, 21100, Italy. andrea.maresca@uninsubria.it.
authors.forename: Andrea Maria
authors.initials: AM
authors.lastname: Maresca
authors.affiliation: Research Center on Dyslipidemia, University of Insubria, Varese, Italy. laura.schembri@uninsubria.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Schembri
authors.affiliation: Research Center on Dyslipidemia, University of Insubria, Varese, Italy. emanuela.rasini@uninsubria.it.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Rasini
authors.affiliation: Research Center on Dyslipidemia, University of Insubria, Varese, Italy. francesco.dentali@uninsubria.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dentali
authors.affiliation: Research Center on Dyslipidemia, University of Insubria, Varese, Italy. alessandro.squizzato@uninsubria.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Squizzato
authors.affiliation: Biometry and Clinical Epidemiology, Research Department, Foundation IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy. catherine.klersy@libero.it.
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.affiliation: Research Center on Dyslipidemia, University of Insubria, Varese, Italy. lalu86@tiscali.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Robustelli Test
authors.affiliation: Research Center on Dyslipidemia, University of Insubria, Varese, Italy. mongiardi@gmail.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Mongiardi
authors.affiliation: Research Center on Dyslipidemia, University of Insubria, Varese, Italy. leonard.campiotto@uninsubria.it.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Campiotti
authors.affiliation: Research Center on Dyslipidemia, University of Insubria, Varese, Italy. walter.agen@uninsubria.it.
authors.forename: Walter
authors.initials: W
authors.lastname: Ageno
authors.affiliation: Research Center on Dyslipidemia, University of Insubria, Varese, Italy. anna.grandi@uninsubria.it.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Grandi
authors.affiliation: Research Center on Dyslipidemia, University of Insubria, Varese, Italy. marco.cosentino@uninsubria.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Cosentino
authors.affiliation: Research Center on Dyslipidemia, University of Insubria, Varese, Italy. franca.marino@uninsubria.it.
authors.forename: Franca
authors.initials: F
authors.lastname: Marino
mesh_terms: D000328:Adult; D001054:Apolipoproteins A / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism; D000069059:Atorvastatin / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D050171:Dyslipidemias / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001054:Apolipoproteins A; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C508609:IL10 protein, human; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014280:Triglycerides; D016753:Interleukin-10; D002097:C-Reactive Protein; D000069059:Atorvastatin
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