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Galectin-3 in heart failure

From biomarker to target for therapy
PhD ceremony:Mr A.R. (Rogier) van der Velde
When:January 11, 2017
Supervisors:R.A. (Rudolf) de Boer, prof. dr. W.H. (Wiek) van Gilst
Co-supervisor:dr. H.H.W. (Herman) Sillje
Where:Academy building RUG
Faculty:Medical Sciences / UMCG

This thesis describes the role of galectin-3 in heart failure. Galectin-3 is a protein that is secreted in our body during inflammation and tissue damage. It is released into the blood stream and can be measured with a blood test. As a biomarker, galectin-3 can be used for risk stratification in patients with heart failure. In our studies we showed that repeated measurements provide incremental prognostic information. Furthermore, galectin-3 is a marker of subclinical disease: it can be used to identify subjects in the general population who are likely to develop heart failure in the future. Galectin-3 is also involved in cardiac fibrosis and is released after myocardial infarction. Baseline galectin-3 measurements in patients with a myocardial infarction predict infarct size and cardiac function.

Another goal of this thesis was to further unravel galectin-3 biology. We showed that galectin-3 levels increase upon severe hypertension or micro-albuminuria. In addition, renal function is an important determinant of the present galectin-3 level. Furthermore, blood group also determines galectin-3 level. Possibly, the biological activity of galectin-3 is regulated by glycosylation, the addition of sugar groups.

The most important feature of galectin-3 is to serve as a target for therapy. Pectins, which are complex sugars extracted from natural food sources, are able to inhibit galectin-3-mediated effects. Administration of pectins in an animal model attenuated cardiac fibrosis and preserved cardiac function. The concept of galectin-3 inhibition could be an interesting addition to the current heart failure treatment regimen.