The Diagnostic and Prognostic Value of Plasma Galectin 3 in HFrEF Related to the Etiology of Heart Failure

Abstract

Aim: The aim of present study is to evaluate the diagnostic and prognostic value of plasma galectin 3 (Gal-3) for HF originating from different causes. Methods: We investigated the plasma levels and expression of Gal-3 in cardiac tissues in two transgenic (TG) strains of mice with cardiomyocyte-restricted overexpression of either β2- adrenergic receptor (β2- AR TG) or Mammalian sterile 20-like kinase 1 (Mst1-TG) in the present study. Additionally, 166 patients suffering from heart failure with reduced ejection fraction (HFrEF) in two hospitals within the Shaanxi province were examined in this study. All these patients were treated according to the Chinese HF guidelines of 2014; subsequently, they were followed up for 50 months, and we analyzed the prediction value of baseline Gal-3 to endpoints in these patients. Results: Gal-3 was localized in the cytoplasm and nucleus of cardiomyocytes, often formed aggregates in Mst1-TG mice. Extracellular Gal-3 staining was uncommon in Mst1-TG hearts. However, in β2-AR TG mice, although Gal-3 was also expressed in myocardial cells, it was more highly expressed in interstitial cells (e.g., fibroblasts and macrophages). Plasma Gal-3 was comparable between nTG and Mst1-TG mice. However, plasma Gal-3 was higher in β2-AR TG mice than in nTG mice. In the cohort of HFrEF patients, the median plasma Gal-3 concentration was 158.42 pg/mL. All participants were divided into two groups according to Gal-3 levels. Patients with Gal-3 concentrations above the median were older, and had lower plasma hemoglobin, but higher plasma creatinine, tissue inhibitor of metalloproteinases 1 (TIMP-1), left ventricular end systolic diameter (LVESD), left ventricular end-systolic volumes (LVESV) and end-diastolic, as well as left ventricular end-diastolic volumes (LVEDV). Spearman correlation analysis revealed that Gal-3 was positively correlated with TIMP-1 (r = 0.396, P < 0.001), LVESV (r = 0.181, P = 0.020) and LVEDV (r = 0.190, P = 0.015). The 50-month clinical follow-up revealed 43 deaths, 97 unplanned re-hospitalizations, and 111 composite endpoint events. Cox analysis demonstrated that although Gal-3 did not provide any prognostic value in either total-HF subjects or coronary-heart-disease (CHD) patients, it did provide prognostic value in non-CHD patients. Conclusion: Although plasma Gal-3 is associated with TIMP-1 and echocardiographic parameters, the diagnostic and prognostic value of Gal-3 in HFrEF is determined by the etiology of HF.

Keywords: diagnostic; etiology; galectin-3; heart failure; prognosis; risk factor.

Figure 1

Plasma concentration of Gal-3 from nTG, Mst1-TG, and β2-AR-TG hearts in mice. Gal-3, galectin-3; nTG: non-transgenic mice; b2-AR TG, β2- adrenergic receptor transgenic; Mst1-TG, Mammalian sterile 20-like kinase 1 transgenic.

Figure 2

Immunofluorescent staining of LV sections from wild-type, Mst1-Tg, and β2-AR-Tg hearts in mice. Gal-3 staining: red fluorescence. Merged images also show cell boundaries in green (i.e., wheat-germ agglutinin-FITC staining).

Figure 3

Correlations of serum Gal-3 levels with TIMP-1, LVEDV, and LVESV in HF patients. (A) Correlation of Gal-3 with TIMP-1. (B) Correlation of Gal-3 with LVESV. (C) Correlation of Gal-3 with LVEDV. Gal-3, galectin-3; LVESV, left ventricular end systolic volume; LVEDV, left ventricular end diastolic volume.

Figure 4

Kaplan–Meier survival curves according to baseline plasma Gal-3 levels in all HF subjects. (A) Death rates according to higher of lower baseline plasma Gal-3 levels. (B) Re-hospitalization rate according to higher of lower baseline plasma Gal-3 levels. (C) Composite-endpoint event rates according to higher of lower baseline plasma Gal-3 levels. Gal-3, Galectin-3.

Figure 5

Kaplan–Meier survival curves according to baseline plasma Gal-3 levels in non-CHD subjects. (A) Death rates according to higher of lower baseline plasma Gal-3 levels. (B) Re-hospitalization rates according to higher of lower baseline plasma Gal-3 levels. (C) Composite-endpoint event rates according to higher of lower baseline plasma Gal-3 levels. Gal-3, Galectin-3.