Galectin-3

Galectin-3 is a carbohydrate-binding lectin whose expression is associated with inflammatory cells including macrophages, neutrophils, and mast cells.

- Concentrations of galectin-3 have been used to predict adverse remodeling after a variety of cardiac insults.

- Galectin-3 is a biomarker that appears to be actively involved in both the inflammatory and some fibrotic pathways.

- Galectin-3 is member of the protein family known as galectins. Galectins bind to certain carbohydrates.

Galectin-3 has been linked to cardiovascular physiological processes including the following:

- myofibroblast proliferation, 

- tissue repair,

- fibrogenesis

- and cardiac remodeling in the setting of heart failure. 

Galectin-3 interacts with carbohydrates, such as N-acetyllactosamine, certain cell surface receptors (such as macrophage CD11b/CD18) and extracellular receptors (such as collagen). Galectins play an important and complex role in intracellular pathways and disease mechanisms. 

Galectin-3 levels reflect the presence of specific underlying disease processes and are not affected by the degree of decompensation. Hence galectin-3 levels, once elevated, remain generally constant and do not fluctuate with signs and symptoms of heart failure. Although certain medical and device treatments appear to be effective in people with elevated galectin-3, galectin-3 plasma levels are generally not affected by these treatments.

What is heart failure?

Heart failure is a complex cardiovascular disorder with a variety of etiologies and heterogeneity with respect to the clinical presentation of the people. 

Heart failure is significantly increasing in prevalence with an aging population and is associated with high short- and long-term mortality rate. Over 80% of people diagnosed and treated for acute heart failure syndromes in the emergency department are readmitted within the forthcoming year, incurring costly treatments and therapies.

The development and progression of heart failure is a clinically silent process until manifestation of the disorder, which typically occurs late and irreversibly into its progression. Mechanistically, heart failure, whether due to systolic or diastolic dysfunction, is thought to progress primarily through adverse cardiac remodeling and fibrosis in response to cardiac injury and/or stress.

Risk assessment:

Galectin-3 concentrations may be categorized into 3 risk categories, substantiated by results from several large chronic heart failure studies:

< or =17.8 ng/mL (low risk)
17.9-25.9 ng/mL (intermediate risk)
>25.9 ng/mL (higher risk)

Additional notes:

- Galectin-3 has not been shown to be useful in the acute diagnosis of heart failure, and natriuretic peptides (BNP or NT-proBNP) should be utilized for this purpose.

- Hemolysis has been shown to interfere with the galectin-3 assay due to intracellular release of galectin-3. Specimens that are visibly hemolyzed will be rejected.

- Heterophile antibodies, in particular human-antimouse antibodies in human serum, may cause falsely elevated galectin-3 results. Heterophile antibodies may react with reagent immunoglobulins and subsequently interfere with in vitro immunoassays. People routinely exposed to animals or to animal serum products can be prone to this interference and anomalous high or low values can be observed.

- People with high concentrations of rheumatoid factor, as well as other autoimmune disorders, may also yield falsely elevated results and should be interpreted with caution.

- Levels of galectin-3 in blood may be increased in People with certain forms of advanced cancer and other conditions associated with organ fibrosis. Galectin-3 results should be interpreted with caution in such patients. 

- Presence of human antimouse antibodies (HAMA) or rheumatoid factor (RF) may interfere with the galectin-3 assay, which could cause falsely elevated results. 

- The galectin-3 assay should not be used in people with known HAMA or RF. 

- Galectin-3 results should be interpreted with caution in patients with a history of therapeutic use of murine monoclonal antibodies (IgG) or their fragments or in those who have known autoimmune disorders.

Specimens with high levels of γ-globulins (>2.5 g/dL) may cause false elevation in results. Galectin-3 results from patients with diseases associated with hyperglobulinemia, such as multiple myeloma, should be interpreted with caution.

Galectin-3 levels >17.8 ng/mL are present in a proportion of patients with NYHA class II-IV. Such elevated levels are associated with a more progressive form of heart failure resulting in an increased hazard for death or hospitalization.

NYHA Classification - The Stages of Heart Failure:

Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc.
Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity.
Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20—100 m).Comfortable only at rest.
Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.

References:
https://pubmed.ncbi.nlm.nih.gov/20153309/
https://pubmed.ncbi.nlm.nih.gov/21189092/
https://pubmed.ncbi.nlm.nih.gov/20425490/
https://pubmed.ncbi.nlm.nih.gov/19324966/
https://pubmed.ncbi.nlm.nih.gov/20130888/
https://pubmed.ncbi.nlm.nih.gov/18503956/
https://pubmed.ncbi.nlm.nih.gov/15520318/
https://pubmed.ncbi.nlm.nih.gov/23395934/
https://pubmed.ncbi.nlm.nih.gov/27677964/
https://pubmed.ncbi.nlm.nih.gov/28079145/
https://pubmed.ncbi.nlm.nih.gov/25824247/
https://pubmed.ncbi.nlm.nih.gov/24890535/
https://pubmed.ncbi.nlm.nih.gov/26582585/
https://pubmed.ncbi.nlm.nih.gov/27525318/