Abstract:Heart failure (HF) is a serious disease syndrome characterized by elevated proinflammatory cytokines and inflammatory mediators presume to have significant contribution on disease progression. Galectins are carbohydrate-binding proteins responsible of various physiological functions. Role of galectins in heart failure has been ill-defined. In the present case-controls study, 136 patients clinically diagnosed with heart failure and 125 healthy Chinese controls were recruited. Levels of galec-
“…al. [14] , who also demonstrated the negative correlation between the concentration of TGFβ and galectin-3 in blood in patients with CHF [14] . Fig.…”
Section: Discussionmentioning
confidence: 96%
“…In the pathogenesis of ICMP, the role of cardiomyocyte apoptosis, extracellular matrix (ECM) destruction with the participation of matrix metalloproteinases (MMPs), matrix formation in the presence of transforming growth factor-beta (TGFβ), microvascular dysfunction, synthesis of collagens with different properties, autoimmune and other mechanisms is being discussed [4] , [5] , [6] , [7] . Galectin-3 is considered as a marker of myocardium damage, fibrosis and unfavorable course of CHD [8] , [9] , [10] , [11] , [12] , [13] , [14] . At the same time, it is known that at different stages of the post-infarct period, the leading positions in the mechanisms of remodeling of the affected myocardium are occupied by macrophages attracted to the focus by chemoattractants, for example, monocyte chemotactic factor (MCP-1).…”
Aims
To identify an imbalance of cardiac remodeling mediators and monocytes subpopulation in blood, distribution of myocardium macrophages in patients with ischemic cardiomyopathy (ICMP).
Methods
The study engaged 30 patients with ICMP, 26 patients with coronary heart disease (CHD) without ICMP, 15 healthy donors. Concentrations of TGFβ, MMP-9, MCP-1, galectin-3 were measured in plasma of blood from the coronary sinus and peripheral blood in CHD patients, as well as in peripheral blood in healthy donors, by enzyme immunoassay method. The ration of classical, intermediate, non-classical, transitional monocytes in peripheral blood of patients and healthy donors was assessed by flow cytometry (expression CD14, CD16); the content of CD68+ macrophages in myocardium – by immunohistochemistry method.
Results
In both samples of blood, the content of galectin-3 in patients with ICMP was higher than in CHD patients without ICMP and the level of TGFβ was comparable between the groups. At ICMP, the concentration of MMP-9 in sinus blood was higher than that in CHD patients without ICMP in whom an excess of MCP-1 in the general blood flow was determined. The density of distribution of CD68+ cells in the myocardium in patients with ICMP was higher in the perianeurysmal zone than in the right atrium appendage. ICMP was characterized by a deficiency of non-classical monocytes, and CHD without ICMP – by an excess of intermediate cells in peripheral blood.
Conclusion
Myocardium remodeling at ICMP is mediated by not so much TGFβ but intracardiac galectin-3, which determines the subpopulation composition of blood monocytes.
“…al. [14] , who also demonstrated the negative correlation between the concentration of TGFβ and galectin-3 in blood in patients with CHF [14] . Fig.…”
Section: Discussionmentioning
confidence: 96%
“…In the pathogenesis of ICMP, the role of cardiomyocyte apoptosis, extracellular matrix (ECM) destruction with the participation of matrix metalloproteinases (MMPs), matrix formation in the presence of transforming growth factor-beta (TGFβ), microvascular dysfunction, synthesis of collagens with different properties, autoimmune and other mechanisms is being discussed [4] , [5] , [6] , [7] . Galectin-3 is considered as a marker of myocardium damage, fibrosis and unfavorable course of CHD [8] , [9] , [10] , [11] , [12] , [13] , [14] . At the same time, it is known that at different stages of the post-infarct period, the leading positions in the mechanisms of remodeling of the affected myocardium are occupied by macrophages attracted to the focus by chemoattractants, for example, monocyte chemotactic factor (MCP-1).…”
Aims
To identify an imbalance of cardiac remodeling mediators and monocytes subpopulation in blood, distribution of myocardium macrophages in patients with ischemic cardiomyopathy (ICMP).
Methods
The study engaged 30 patients with ICMP, 26 patients with coronary heart disease (CHD) without ICMP, 15 healthy donors. Concentrations of TGFβ, MMP-9, MCP-1, galectin-3 were measured in plasma of blood from the coronary sinus and peripheral blood in CHD patients, as well as in peripheral blood in healthy donors, by enzyme immunoassay method. The ration of classical, intermediate, non-classical, transitional monocytes in peripheral blood of patients and healthy donors was assessed by flow cytometry (expression CD14, CD16); the content of CD68+ macrophages in myocardium – by immunohistochemistry method.
Results
In both samples of blood, the content of galectin-3 in patients with ICMP was higher than in CHD patients without ICMP and the level of TGFβ was comparable between the groups. At ICMP, the concentration of MMP-9 in sinus blood was higher than that in CHD patients without ICMP in whom an excess of MCP-1 in the general blood flow was determined. The density of distribution of CD68+ cells in the myocardium in patients with ICMP was higher in the perianeurysmal zone than in the right atrium appendage. ICMP was characterized by a deficiency of non-classical monocytes, and CHD without ICMP – by an excess of intermediate cells in peripheral blood.
Conclusion
Myocardium remodeling at ICMP is mediated by not so much TGFβ but intracardiac galectin-3, which determines the subpopulation composition of blood monocytes.
“…Therefore, future studies should further investigate the roles and mechanisms of Gal-3 in myocardial fibrosis and HF. Although there have been many studies investigating the relationship between blood levels of Gal-3 and mortality in HF patients (40)(41)(42), the predictive value of Gal-3 for the prognosis of HF remains to be illusive (43). Recently, the PARADIGM-HF trial revealed that baseline and eight-month changes in serum Gal-3 levels did not predict outcomes in HFrEF patients (44).…”
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.
“…Although there have been many studies investigating the relationship between blood levels of Gal-3 and mortality in HF patients [35][36][37] , the predictive value of Gal-3 for the prognosis of HF remains to be illusive [38] . Recently, the PARADIGM-HF trial revealed that baseline and eight-month changes in serum Gal-3 levels did not predict outcomes in HFrEF patients [32] .…”
Background: Although plasma galectin 3 (Gal-3) has been investigated in many previous studies, its prognostic value has not yet been determined. However, many studies had found that plasma and cardiac levels of Gal-3 are different within different animal models of heart failure (HF). Aim: The aim of the present study was to evaluate the prognostic value of plasma Gal-3 for HF originating from different causes. Methods: We examined 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. Age-matched non-transgenic (nTG) littermates were used as controls. Additionally, 166 patients suffering from heart failure with reduced ejection fraction (HFrEF) in two hospitals within the Shaanxi province were included in the present study. These patients were treated in accordance with the Chinese HF guidelines of 2014. Subsequently, these patients were followed up for 50 months, during which we analyzed the prediction value of baseline Gal-3 to endpoints in these patients via Cox and Kapla-Meir analyses. Results: Gal-3 was localized in the cytoplasm and nucleus of cardiomyocytes, often forming aggregates in Mst1TG 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 is 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 nTG mice. In HFrEF patients cohort, the median Gal-3 concentration was 158.42 pg/mL. All participants were divided into two groups according to their Gal-3 levels. There were no statistical differences between the two groups in terms of gender, hypertension history, diabetes history, treatments, death, re-hospitalization and composite endpoint events. However, patients with Gal-3 plasma concentrations above the median were older (P=0.043), had lower plasma hemoglobin(P = 0.002), but higher plasma creatinine (P=0.011), tissue inhibitor of metalloproteinases 1 (TIMP-1)(P=0.002), left ventricular end systolic diameter (L VESD) (P = 0.036), left ventricular end-systolic volumes (LVESV) (P=0.043)and end-diastolic, and left ventricular end-diastolic volumes (LVEDV) (P=0.036).Spearmen 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). During a 50-month follow-up, 43 deaths, 97 unplanned re-hospitalizations, and 111 composite endpoint events occurred. 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 concentrations of Gal-3 were associated with TIMP-1 and echocardiographic parameters, the prognostic value of plasma Gal-3 in HFrEF depended on the etiology of HF.
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