Changes of naturally occurring CD4(+)CD25(+) FOXP3(+) regulatory T cells in patients with acute coronary syndrome and the beneficial effects of atorvastatin treatment.
To determine the number and function of naturally occurring CD4(+)CD25(+)FOXP3(+) regulatory T cells (nTregs) in patients with acute coronary syndrome (ACS) and to determine the effects of a low dose of atorvastatin treatment (20 mg/day) on nTregs.Patients with ACS were randomly divided into a group receiving conventional therapy (n = 60) or conventional therapy supplemented with atorvastatin (20 mg/day) (n = 60). A group of healthy volunteers that did not suffer from ACS was used as controls (n = 60). T lymphocytes were isolated from ACS patients, both before and 4 weeks after treatment, or control patients and the percentage of nTregs was determined by flow cytometry. Serum levels of cytokines were determined by enzyme-linked immunosorbent assays. A mixed lymphocyte reaction was used to determine the ability of nTregs to inhibit proliferation of effector T cells. Quantitative PCR and Western blot were used to analyze (forkhead box P3) FOXP3 mRNA transcript levels and the expression of FOXP3 protein.In ACS patients, the percentage and inhibitory properties of nTregs were reduced, IFN-γ and hsCRP levels were increased, and IL-10 and TGF-β1 levels were lowered. Atorvastatin treatment increased the percentage and inhibitory ability of nTregs, decreased serum IFN-γ and hsCRP levels, and decreased IL-10 and TGF-β1 levels, as compared with the non-atorvastatin group.Our findings suggest that nTregs play an atheroprotective role in atherosclerosis. The inhibitory effects of atorvastatin on inflammation in ACS may be due to its beneficial effects on nTregs and restoration of immune homeostasis.
Department of Cardiology, Renmin Hospital of Wuhan University.
Zhi Xiao
ZX
Wang
Chong Quan
CQ
Wang
Xiao Yan
XY
Li
Yan
Y
Ding
Gao Ke
GK
Feng
Xue Jun
XJ
Jiang
D054058:Acute Coronary Syndrome / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D015704:CD4 Antigens / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D015704:CD4 Antigens; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053645:Interleukin-2 Receptor alpha Subunit; D011758:Pyrroles; D012333:RNA, Messenger; D000069059:Atorvastatin