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

ABSTRACT

BACKGROUND: TGF-ß1 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-ß1) 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-ß1 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 CD4+CD25+FoxP3+ Tregs. RESULTS: PBMCs in patients with CHF expressed higher levels of TGF-ß1 compared to controls. Post-stimulation levels of TGF-ß1 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-ß1 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.