The role of galectin-3 in cardiac remodeling and fibrogenesis

PhD ceremony: Ms. L. Yu, 9.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: The role of galectin-3 in cardiac remodeling and fibrogenesis

Promotor(s): prof. W.H. van Gilst

Faculty: Medical Sciences

Galectin-3 (Gal-3) is a blood plasma protein that has predictive value for the prognosis of heart failure (HF), with high values in poor prognosis. In addition to this predictive function, Gal-3 also contributes to the development of HF, in particular the process of formation of connective tissue fibrosis which leads to a stiffer heart. This fibrotic process also plays a role in the damage to other organs, such as chronic kidney disease. Therapy for these disorders that specifically target Gal-3 is considered, however, they are poorly investigated. In this thesis the role of Gal-3 in the development of fibrosis during HF and chronic kidney disease is discussed. In addition, we evaluated whether Gal-3 is a relevant therapeutic target in cardiac remodeling and HF. Herein, we employed a mouse model where the Gal-3 gene has been removed. Furthermore, we also assessed HF development in rats that were administered a specific molecular compound that Gal-3 can recognize, bind to and thereby inactivate. In both mice and rat models, we showed that the inactivation of Gal-3 can reduce the progression of HF and even slightly cause HF regression which also improved overall cardiac function. In addition, because cardiovascular diseases are often associated with renal insufficiency, Gal-3 targeted intervention was also investigated in hypertensive rats. Renal function was clearly improved in these animals. In conclusion, blocking Gal-3 with such pharmaceutical substances proves a promising therapeutic target, leading to further improvements in cardiovascular and renal function for patients suffering from congestive heart failure and renal insufficiency.