Purpose: It has been proposed that galectin-3 (Gal-3) may be a pathogenic factor and a biomarker of myocardial fibrosis in patients with heart failure (HF). The aim of this study was to analyze whether Gal-3 is associated with myocardial fibrosis in patients with chronic stable HF.
Methods: Endomyocardial biopsies and blood samples from non-diabetic, hypertensive patients without ischemic heart disease and with HF (n=39), and necropsies and blood samples from 7 and 20 control subjects, respectively, were studied. Left ventricular (LV) morphology and function were assessed by echocardiography. The area of the myocardium occupied by total collagen (CVF) was assessed by image analysis in Picrosirius Red-stained sections. Collagen type I and III CVFs were analyzed in sections immunostained for collagen type I or III. Gal-3 and collagen type I and III mRNA and protein expression were quantified by real time RT-PCR and western blot, respectively. Plasma Gal-3 and amino-terminal propeptide of brain natriuretic peptide (NT-proBNP) were determined by ELISA. Plasma aldosterone was measured by radioimmunoassay.
Results: Myocardial Gal-3 protein (P<0.005) and mRNA (P<0.05) were increased in patients compared to controls. Similarly, total CVF, collagen type I and III CVFs, as well as collagen type I and III protein levels, were increased (all P<0.001) in patients compared to control subjects. Myocardial Gal-3 protein was not correlated with neither total CVF, nor with collagen type I and III CVFs, mRNA and protein in patients. Plasma Gal-3 was increased (P<0.001) in patients compared to controls. Although plasma Gal-3 was correlated with myocardial Gal-3 (r=0.455, P<0.05) in patients, its concentration was not higher in blood from the coronary sinus than in blood from a peripheral vein. Plasma Gal-3 was not correlated with neither total CVF, nor with collagen type I and III CVFs, mRNA and protein in patients. Additionally, no associations were found between myocardial or plasma Gal-3 and parameters assessing LV morphology and function in patients. Interestingly, plasma Gal-3 was directly associated with plasma aldosterone (r=0.286, P<0.05).
Conclusions: These findings show that although an excess of cardiac and systemic Gal-3 is present in patients with HF of hypertensive origin, this molecule is not associated with myocardial fibrosis in these patients. Further studies are necessary to unveil the pathophysiological role of an excess of Gal-3 in these patients.