Gene Expression and Levels of TGF-B in PBMC Is Associated with Severity of Symptoms in Chronic Heart Failure.

BACKGROUND

TGF-β1 is known to promote cardiac remodeling and fibrosis during Congestive Heart Failure (CHF). In this study, an attempt was made to investigate expression of Transforming Growth Factor beta1 (TGF-β1) and relative expansion or contraction of regulatory T-cell (Tregs) population in peripheral blood of patients with Chronic Heart Failure (CHF).

METHODS

Real-time PCR assay was used to investigate expression and post-stimulation levels of TGF-β1 in cell culture supernatant of Peripheral Blood Mononuclear Cells (PBMC) of 42 patients with CHF and 42 controls. Flow cytometry was used to identify relative counts of CD4CD25FoxP3 Tregs.

RESULTS

PBMCs in patients with CHF expressed higher levels of TGF-β1 compared to controls. Post-stimulation levels of TGF-β1 expression were significantly higher in New York Heart Association (NYHA) functional class IV patients compared to stage I patients. Tregs were significantly expanded in PBMC in CHF, while the CD4 helper T-cells were unchanged. Treg expansion was more significant in NYHA functional class I patients compared to class IV patients.

CONCLUSION

Expansion of Treg population in CHF provides an extrinsic source for TGF-β1 production to induce reactive fibrosis and cardiac remodeling. Relative decrease in Treg population at advanced stages of CHF is indicative of a loss of regulatory characteristics in these cells and unopposed proinflammatory milieu.