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.
Highlights
Heart failure (HF) is a disease of high morbidity and mortality regardless of therapies [1, 2]
In β2-AR TG mice, Galectin 3 (Gal-3) was expressed in myocardial cells, it was more highly expressed in interstitial cells
In keeping with our previous findings, the plasma Gal-3 concentration in β2-AR-TG mice was significantly elevated vs. nTG mice, whereas Mammalian sterile 20-like kinase 1 transgenic (Mst1-TG) mice showed no change in plasma Gal-3 concentration compared with that of respective nTG group (Figure 1)
Summary
Heart failure (HF) is a disease of high morbidity and mortality regardless of therapies [1, 2]. As indicators of pathological processes and responses to therapeutic interventions, circulating blood biomarkers have been increasingly studied due to their noninvasive determinations that tend to be sufficiently sensitive and accurate. Due to different etiologies and underlying pathophysiological processes, HF was a heterogeneous disease. There are many different available biomarkers [e.g., NTproBNP [3], GDF-15 [4]], the diagnosis and prognostic values of these biomarkers were discordant. Many previous studies have demonstrated elevated plasma concentrations of Gal-3 in both acute and chronic HF, the prognostic value of Gal-3 in predicting re-hospitalization and mortality has not yet been determined. Zhao et al [16] and we [17] found that plasma and cardiac levels of Gal-3 were different across distinct HF caused by different etiologies in experimental animals. It seems reasonable to hypothesize that the diagnostic and prognostic
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