Plasma and Cardiac Galectin-3 in Patients With Heart Failure Reflects Both Inflammation and Fibrosis

Abstract

Background— Galectin (Gal)-3 is a β-galactoside-binding lectin and currently intensely studied as a biomarker in heart failure. Gal-3 also exerts proinflammatory effects, at least in extracardiac tissues. Objective of this study was to characterize the relationship of plasma and myocardial Gal-3 levels with cardiac fibrosis and inflammation in patients with nonischemic dilated cardiomyopathy and inflammatory cardiomyopathy (iCMP). Methods and Results— Endomyocardial biopsies and blood samples were obtained from patients with newly diagnosed cardiomyopathy and clinical suspicion of myocarditis. According to histopathologic findings, patients were classified as having dilated cardiomyopathy (n=40) or iCMP (n=75). Cardiac fibrosis was assessed histologically on endomyocardial biopsy sections. In patients with iCMP, myocardial Gal-3 expression significantly correlated with inflammatory cell count on endomyocardial biopsy ( r =0.56; P <0.05). In contrast, an inverse association was observed between myocardial Gal-3 expression and cardiac fibrosis in patients with iCMP ( r =−0.59; P <0.05). In patients with dilated cardiomyopathy, myocardial Gal-3 expression correlated with cardiac fibrosis on left ventricular biopsy ( P =0.63; P <0.01). Of note, in both groups, plasma Gal-3 levels did not correlate with myocardial Gal-3 levels or left ventricular fibrosis, whereas a positive correlation between plasma Gal-3 levels and inflammatory cell count on endomyocardial biopsy was observed in patients with iCMP. Conclusions— The present study suggests that myocardial Gal-3 can be considered as a possible marker for both cardiac inflammation and fibrosis, depending on the pathogenesis of heart failure. However, circulating concentrations of Gal-3 do not seem to reflect endomyocardial Gal-3 levels or cardiac fibrosis.

Novel heart failure biomarkers: why do we fail to exploit their potential?

“…In some clinical studies, Gal-3 plasma levels were not directly related to specific cardiac parameters of HF, including echocardiographic parameters [59]. Moreover, a study in which endomyocardial biopsies were taken from dilated and inflammatory cardiomyopathy patients revealed that Gal-3 levels in these biopsies did not reflect plasma Gal-3 levels [60]. Finally, in HF patients with elevated Gal-3 plasma levels prior to heart transplantation, the levels did not decline post-transplantation, which indicated that other non-cardiac sources were predominantly responsible for elevated Gal-3 plasma levels in these patients [61].…”

Biomarkers in patients with myocardial fibrosis

“…In patients with inflammatory cardiomyopathy (iCMP) and nonischemic dilated cardiomyopathy, the level of myocardial Gal-3, but not circulating concentrations of Gal-3, was found as a possible marker for cardiac fibrosis, depending on pathogenesis of heart failure [23]. In the study of 259 blood samples and endomyocardial biopsies from heart failure patients, plasma myocardial mRNA and protein expression of Gal-3 were measured.…”

Up-to-date clinical approaches of biomarkers’ use in heart failure

“…In patients with acute HF and acutely decompensated HF galectin-3 was associated with NTproBNP levels and the estimated glomerular filtration rate (GFR) but not with age and serum cardiac troponins (Besler et al, 2017). Nowadays galectin-3 is concerned the predictive biomarker for all-cause mortality, CV mortality and HFrelated clinical outcomes in patients with established HF.…”

“…Additionally, there is a huge list of the diseases associated with increased level of NPs beyond HF development ( Table 2). Although galectin-3 is an independent predictor of all-cause mortality, CV death and occurrence of HF, there is an inverse relationship between serum galectin-3 and estimated glomerular filtration rate (Besler et al, 2017). Accordingly, lowered kidney clearance should be taken into consideration, when data of galectin-3 measurement are interpreted.…”