The effect of HMG-CoA reductase inhibitors on naturally occurring CD4+CD25+ T cells

Mausner-Fainberg, Karin; Luboshits, Galia; Mor, Adi; Maysel-Auslender, Sophia; Rubinstein, Ardon; Keren, Gad; George, Jacob

doi:10.1016/j.atherosclerosis.2007.07.031

Cited by 212 publications

(152 citation statements)

References 35 publications

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“…Statins have a number of immunomodulatory effects and modulate immune system-mediated activities, including inhibiting the production of inflammatory cytokines associated with immunity, T lymphocyte activation, mononuclear cell proliferation and antigen-presenting capacity (24,27). Extensive evidence also indicated that statins reduce the production of inflammatory cytokines and stabilize vulnerable plaques in atherosclerosis, in part because of their immunomodulatory mechanism (18,19).…”

Section: Discussionmentioning

confidence: 99%

Statins Induce the Accumulation of Regulatory T Cells in Atherosclerotic Plaque

Xiao

Zhang

et al. 2012

Mol Med

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+ regulatory T cells (Tregs) mediate immune suppression and prevent autoimmune disorders. Recently, Tregs were found to present in atherosclerotic lesions and play an important role in the progression of atherosclerosis. Statins have immunomodulatory properties, and the effect of statins on atherosclerosis depends in part on their immunomodulatory mechanisms. We sought to determine whether statins exhibit an effect on Tregs in atherosclerotic plaques and in peripheral circulation of patients with acute coronary syndrome (ACS). In an in vivo experiment, we induced atherosclerotic plaques in apolipoprotein E-deficient (ApoE

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Section: Discussionmentioning

confidence: 99%

Statins Induce the Accumulation of Regulatory T Cells in Atherosclerotic Plaque

Xiao

Zhang

et al. 2012

Mol Med

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“…19) For example, statins (such as atorvastatin, pravastatin, and simvastatin) increased the number of human Tregs in vitro and increased transcript levels of FOXP3. 20) Treatment with atorvastatin, in particular, has been shown to be superior in preventing and treating cardiovascular disease. [21][22][23] Correlation analysis suggested that Tregs frequency and function positively are correlated with left ventricular ejection fraction, but negatively correlated with left ventricular end-diastolic dimension and Nterminal pro-brain natriuretic peptide (NT-proBNP) in patients with CHF.…”

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confidence: 99%

Changes of Naturally Occurring CD4+CD25+ FOXP3+ Regulatory T Cells in Patients With Acute Coronary Syndrome and the Beneficial Effects of Atorvastatin Treatment

Wang¹,

Wang

Li³

et al. 2015

Int. Heart J.

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SummaryTo determine the number and function of naturally occurring CD4+ 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-β 1 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-β 1 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. (Int Heart J 2015; 56: 163-169)

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“…This phenomenon may be attributed to the reported potential impact of statins on T cells production. In healthy individuals, statins treatment was associated with the induction of transcription factor forkhead box P3 and a subsequent increase in the number of T cells (68). T cells increases have been linked to impaired innate and adaptive immune responses (69,70).…”

Section: Resultsmentioning

confidence: 99%

Clinical Potential of Statins in Prostate Cancer Radiation Therapy

Hutchinson

Marignol

2017

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Abstract. Background The management of prostate cancer is a significant healthcare challenge. Many treatment options exist (1-3), with radiation therapy playing a prominent role. However, the morbidity and cost of treatment are not trivial (4, 5). Although risk classification schemes (6) and nomograms (7) attempt to identify men most likely to benefit from treatment, it remains difficult to balance the risks of disease progression against competing risks of mortality (8). This has resulted in controversy over prostate-specific antigen (PSA) screening (9, 10) and possible overtreatment leading to a decreased quality of life (5, 11). Therefore, it is of great interest to conduct research into cancer prevention strategies (12), identification of men who will benefit most from treatment, and effective therapies that limit treatment-related morbidity of prostate cancer.Statins or 3-hydroxyl-3-methylglutaryl-coenzyme A (HMGCoA) reductase inhibitors are widely used medications for hypercholesterolaemia. The demographics of prostate cancer and hypercholesterolaemia overlap. The prevalence of statin use in this older men population is high-approximately 24 million Americans in 2003-2004 (13). Thus, many prostate cancer patients are likely to have already been prescribed statins at the time of their cancer diagnosis and treatment.Initial interest in the use of statins in prostate cancer stemmed from epidemiological studies that investigated their chemopreventive properties. Two large case-control series reported a 50%-65% reduction in overall prostate cancer risk among statin users compared with non-users (14, 15

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The effect of HMG-CoA reductase inhibitors on naturally occurring CD4+CD25+ T cells

Cited by 212 publications

References 35 publications

Statins Induce the Accumulation of Regulatory T Cells in Atherosclerotic Plaque

Statins Induce the Accumulation of Regulatory T Cells in Atherosclerotic Plaque

Changes of Naturally Occurring CD4<sup>+</sup>CD25<sup>+</sup> FOXP3<sup>+</sup> Regulatory T Cells in Patients With Acute Coronary Syndrome and the Beneficial Effects of Atorvastatin Treatment

Clinical Potential of Statins in Prostate Cancer Radiation Therapy

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