Abstract 5900: Atorvastatin Up-Regulates CD4+CD25+ Regulatory T Cells Function in Patients with Non-Ischemic Chronic Heart Failure
Background: Considerable evidence suggests that immune and inflammatory activation may contribute to chronic heart failure (CHF), and statins can be beneficial in CHF for their anti-inflammatory and immunomodulatory properties. CD4+CD25+ regulatory T cells (Tregs) have been demonstrated to be a key role in the maintenance of self-tolerance via suppressing immune responses, and be associated with various immune disorders for their impaired function. We assessed the hypothesis that the circulating numbers and function of Tregs are deranged and atorvastatin up-regulates the impaired Tregs function in patients with CHF.
Methods: The circulating numbers and suppressive function of Tregs which expressed their master transcription regulator, Foxp3, were analyzed from 48 patients with non-ischemic CHF and 20 healthy donors. To observe the effects of atorvastatin on Tregs, patients with non-ischemic CHF were divided into CHFc group (treated with normal therapy, n=20) and CHFa group (plus with atorvastatin, 10mg/d for 4 weeks, n=28). The frequencies and suppressive function of CD4+CD25+Foxp3+ Tregs were evaluated on admission and 4 weeks later. Furthermore, the numbers and functional properties of Tregs were examined in peripheral blood mononuclear cells cultured with or without atorvastatin in vitro.
Results: CD4+CD25+Foxp3+Tregs in patients with CHF showed significantly lower frequencies (1.41±0.71% vs 5.59±1.73% of CD4+ T cells, P<0.01), lower expression levels of Foxp3, and impaired in vitro suppressive function compared to healthy donors. The frequencies of CD4+CD25+Foxp3+ Tregs expressed high levels of Foxp3 increased (3.58±1.27% of CD4+ T cells in CHFa group vs 1.73±0.59% in CHFc group, P<0.05), which corresponding to increased numbers of Tregs after atorvastatin treatment in vitro. Moreover, atorvastatin promoted conversion of peripheral CD4+CD25− T cells to CD4+CD25+ Tregs and increased their suppressive function to effector T cells.
Conclusion: The numbers of Tregs in patients with CHF are reduced and their function properties are compromised. Atorvastatin significantly up-regulates the impaired Tregs function in patients with CHF in vivo and in vitro, which suggests new therapeutic modalities for maintenance homeostasis of CHF.