Soluble fibrinogen‑like protein 2 levels are decreased in patients with ischemic heart failure and associated with cardiac function

Mol Med Rep. 2021 Aug;24(2):559. doi: 10.3892/mmr.2021.12198. Epub 2021 Jun 10.

Abstract

Soluble fibrinogen‑like protein 2 (sFGL2), as a novel effector of regulatory T cells (Tregs), exhibits immune regulatory activity in several inflammatory diseases. Immune activation and persistent inflammation participate in the progression of ischemic heart failure (IHF). The present study aimed to determine serum sFGL2 levels in patients with IHF and explore the relationship between sFGL2 levels and cardiac function. A total of 104 patients with IHF and 32 healthy controls were enrolled. patients with IHF were further split into subgroups according to the New York Heart Association functional classification or left ventricular ejection fraction (LVEF). Serum sFGL2 levels and peripheral Tregs frequencies were analyzed by ELISA and flow cytometry, respectively. The suppressive function of Tregs was measured by proliferation and functional suppression assays. Serum levels of sFGL2 and circulating Tregs frequencies were significantly decreased in patients with IHF compared with healthy controls. In patients with IHF, sFGL2 levels and Tregs frequencies were decreased with the deterioration of cardiac function. Tregs from patients with IHF exhibited compromised ability to suppress CD4+CD25 T cells proliferation and inflammatory cytokines secretion. Specifically, sFGL2 levels and Tregs frequencies positively correlated with LVEF, whereas negatively correlated with left ventricular end‑diastolic dimension and N‑terminal pro‑brain natriuretic peptide. sFGL2 levels were positively correlated with Tregs frequencies. In conclusion, the reduction of serum sFGL2 levels are associated with the progression of IHF and sFGL2 could be used as a potential indicator for predicting disease severity.

Keywords: adverse ventricular remodeling; ischemic heart failure; regulatory T cells; soluble fibrinogen‑like protein 2.

MeSH terms

  • Aged
  • CD4 Antigens / immunology
  • Female
  • Fibrinogen / immunology
  • Fibrinogen / metabolism*
  • Heart Failure / blood*
  • Heart Failure / diagnosis
  • Heart Failure / immunology
  • Humans
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Male
  • Middle Aged
  • Myocardial Ischemia / blood*
  • Myocardial Ischemia / diagnosis
  • Myocardial Ischemia / immunology
  • ROC Curve
  • T-Lymphocytes, Regulatory / immunology
  • Ventricular Function, Left / immunology

Substances

  • CD4 Antigens
  • FGL2 protein, human
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Fibrinogen

Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant. nos. 81270267 and 81901429).