GALECTIN-3 AS A PHENOTYPICALLY INDICATOR OF CARDIOVASCULAR RISK IN PATIENTS WITH HEART FAILURE
DOI:
https://doi.org/10.14739/2310-1210.2013.6.20822Keywords:
galectin-3, heart failure, clinical outcomes, diagnostic and prognostic valueAbstract
Chronic heart failure is associated with an activation of the immune system characterized among other factors by the cardiac synthesis and serum expression of proinflammatory cytokines.
Galectin-3 is a 31 kDa member of a growing family of beta-galactoside-binding animal lectins, plays an important role in inflammation, fibrosis, and heart failure.. This protein is expressed in a variety of tissues and cell types and is mainly found in the cytoplasm, although, depending on cell type and proliferative state, a significant amount of this lectin can also be detected in the nucleus, on the cell surface or in the extracellular environment. Galectin-3 is secreted from cells by a novel and incompletely understood mechanism that is independent of the classical secretory pathway through the endoplasmic reticulum/Golgi network. Galectin-3 exhibits pleiotropic biological function, playing a key role in many physiological and pathological processes.
Galectin-3, a beta-galactoside binding protein, contains a C-terminal carbohydrate recognition domain (CRD) and an N-terminal domain that includes several repeats of a proline-tyrosine-glycine-rich motif.
Galectin-3 is expressed abundantly by macrophages, but its function in this cell type is not well understood. Results indicate that galectin-3 contributes to macrophage phagocytosis through an intracellular mechanism. Thus, galectin-3 play an important role in adaptive immunity by contributing to phagocytic clearance of microorganisms and apoptotic cells.
Galectin-3 expression was low in the cerebrum, heart, and pancreas, and moderate in the liver, ileum, kidney, and adrenal gland. High expression of galectin-3 was found in the lung, spleen, stomach, colon, uterus, and ovary. These findings suggest that galectin-3 is differentially expressed in a variety of organs.
An early increase in galectin-3 expression identifies failure-prone hypertrophied hearts. Galectin-3, a macrophage-derived mediator, induces cardiac fibroblast proliferation, collagen deposition, and ventricular dysfunction.
Galectinl-3 is required for inflammatory and fibrotic responses to aldosteron in vascular smooth muscle cells in vitro and in vivo, suggesting a key role for Gal-3 in vascular fibrosis.
Recently, a role for galectin-3 in the pathophysiology of heart failure has been suggested. Numerous studies have demonstrated the up-regulation of galectin-3 in hypertrophied hearts, its stimulatory effect on macrophage migration, fibroblast proliferation, and the development of fibrosis.
It was investigated the utility of novel serum markers alone or together with natriuretic peptide testing for diagnosis and short-term prognosis estimation in subjects with acute HF. The NT-proBNP was superior to either apelin or galectin-3 for diagnosis of acute HF, although galectin-3 levels were significantly higher in subjects with HF compared with those without. This data shows potential utility of galectin-3 as a useful marker for evaluation of patients with suspected or proven acute HF. Moreover, the combination of galectin-3 with NT-proBNP was the best predictor for prognosis in subjects with acute HF.
A growing body of evidence links macrophage activation and fibrosis to the pathogenesis of heart failure. Galectin-3 is one of the most likely mediators between macrophage activation and myocardial fibrosis. Galectin-3 is significantly correlated with serum markers of cardiac extracellular matrix turnover in of heart failure patients. This implies a relationship between macrophage activation and ECM turnover in patients with HF.
The latter observation is particularly relevant as cardiac remodelling is an important determinant of the clinical outcome of HF and is linked to disease progression and poor prognosis. Because galectin-3 expression is maximal at peak fibrosis and virtually absent after recovery, routine measurement in patients with HF may prove valuable to identify those patients at highest risk for readmission or death, thus enabling physicians to tailor the level of care to individual patient needs. This review summarizes the most recent advances in galectin-3 research, with an emphasis on the role galectin-3 plays in the development and progression of heart failure.
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