Galectin-3 Inhibition

The intriguing findings related to galectin-3 biology prompted researchers to study a number of ways to block or inhibit galectin-3. Published data describes the effective use of a small peptide; other recent or on-going research includes galectin-3 knock-out mice (mice that no longer have the gene to make galectin-3), use of small interfering RNA (siRNA) that can silence galectin-3 gene activity, and the use of carbohydrate molecules. The studies with carbohydrate molecules take advantage of the fact that galectin-3 has a built-in carbohydrate “switch” that can deactivate galectin-3.

The results of these experiments have been consistent. Galectin-3 blockade results in the prevention or reduction of fibrogenesis, regardless of whether the galectin-3 elevation is triggered by inflammation or through the administration of the galectin-3 protein.

What do we know about existing drugs?

Research is being conducted to investigate if  currently available prescription drugs could be used more effectively in the treatment of patients with galectin-3-mediated heart failure. Current treatment guidelines do not discriminate between the various causes of heart failure. Patients with galectin-3-mediated heart failure should be treated in accordance with current guidelines. Large prospective clinical trials have documented the benefits of aldosterone antagonists (spironolactone and eplerenone) in reducing cardiac fibrosis and improving clinical outcomes. Given the relationship between galectin-3 and fibrosis, and the benefits of aldosterone blockade in reducing fibrosis and adverse remodeling, it may be appropriate to consider aldosterone antagonists for patients with elevated galectin-3. Current practice guidelines recommend addition of low-dose aldosterone antagonists in carefully selected patients with moderately severe or severe HF symptoms and recent decompensation, or with left ventricular dysfunction early after myocardial infarction. A large proportion of these patients are likely to have elevated galectin-3, and the potential use of aldosterone antagonists, in accordance with the guidelines, may be appropriate.

Role of natural pectins

All galectins have a carbohydrate binding site and certain carbohydrate (sugar) molecules that inhibit galectin-3. These galectin-3 binding carbohydrates can be found in pectins, which are large carbohydrate molecules made from plant products, such as citrus peel. Pectins are naturally occurring in fruits and are used in the food industry. Certain pectins, including modified citrus pectin (MCP), are commercially available as a dietary supplement. Animal studies have demonstrated that MCP can inhibit galectin-3. However, there have been no clinical studies to support its use in humans. Although pectins are generally considered safe, it is important for patients to discuss the use of any supplements with their physician.

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Further Reading:

  1. Liu H, D’Ambrosio M, Liao T, et al. N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin Am J Physiol Heart Circ Physiol. 2009;296:H404-12.
  2. Sharma U, Rhaleb NE, Pokharel S, et al. Novel anti-inflammatory mechanisms of N-acetyl-ser-asp-lys-pro in hypertension-induced target organ damage Am J Physiol Heart Circ Physiol. 2008;294:H1226-32.

For a complete list of related readings, please see our Bibliography.