Galectin-3: a Mediator in Heart Failure
Heart failure is a heterogeneous condition, with many different causes and several distinct clinical manifestations. It is one of the few remaining conditions that is described and managed on the basis of signs and symptoms, as opposed to etiology or disease processes. Many conditions that were previously managed by signs and symptoms have now evolved to include disease-modifying therapies. Primarily, this has become possible through our better understanding of underlying disease processes.
The role of galectin-3 in heart failure was a surprise finding. A group of researchers in The Netherlands (Sharma, 2004) studied a proven rat model of heart failure and found that rats with elevated activity of the galectin-3 gene went on to develop heart failure. The researchers performed a series of elegant studies, including one in which the galectin-3 protein was administered in the pericardial space surrounding the heart. This exposure to galectin-3-induced collagen formation in the left ventricle of the heart, and reduced the heart’s ability to pump normally.
These researchers also took biopsies from patients undergoing heart surgery and demonstrated elevated galectin-3 in the hearts of patients with heart failure as compared to those without heart failure. Further, this research has now been complemented these findings, and galectin-3 has emerged as a mediator of a common and progressive form of heart failure.
At this point, it is not known why the galectin-3 gene is activated and leads to a progressive form of heart failure. Evidence suggests the process is often started by cardiac injury, for example, as a result of coronary artery disease (including myocardial infarction), or damage from high blood pressure. In these patients, tissue injury and damage triggers inflammation and a wound healing response. In the majority of patients, this is a beneficial repair mechanism that ends naturally. However, in some patients this fibrosis becomes diffuse and progressive, resulting in changes in the shape and dimensions of the heart. This process is often known as “adverse remodeling” or “remodeling.” This progressive diffuse fibrosis appears to be mediated by elevated galectin-3 levels.
Importance of Galectin-3-Mediated Heart Failure
Heart failure occurs when the heart is unable to meet the demands of the body; it has many different underlying causes and can occur at any age.
Galectin-3-mediated heart failure is common and represents approximately 30% of mild to moderate heart failure (New York Heart Association class II and III). Contrary to many forms of heart failure, galectin-3-mediated heart failure is inherently progressive, causing patients to more rapidly lose cardiac function and increase their risk of hospitalization and death. Because galectin-3 increases the risk of hospitalizations, approximately two-thirds of patients hospitalized for heart failure have galectin-3-mediated heart failure. The mortality of galectin-3-mediated heart failure is high and comparable to invasive cancers.
Galectin-3 in Heart Failure with Preserved Ejection Fraction
When heart failure predominantly affects the contraction of the left side of the heart, it is referred to as systolic heart failure. When it affects the relaxation of the heart, it is referred to as diastolic heart failure or heart failure with preserved contraction. Diastolic heart failure is also referred to as heart failure with preserved ejection fraction. Galectin-3-mediated heart failure appears to be equally common in systolic and diastolic heart failure, (Figure 1).
Further Reading:
- de Boer RA, Voors AA, Muntendam P, et al. Galectin-3: a novel mediator of heart failure development and progression. Eur J Heart Fail. 2009;11:811-17.
- deFilippi CR, Felker GM. Galectin-3 in heart failure-linking fibrosis, remodeling, and progression. US Cardiology. 2010;7:67-70.
- Sharma UC, Pokharel S, van Brakel TJ, et al. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation. 2004;110:3121-28.
For a complete list of related readings, please see our Bibliography.
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