Grant: Operating Grant

Many chronic cardiac diseases leading to heart failure are characterized by abnormally large hearts (hypertrophy) and also increased fibrous tissue (fibrosis). Our previous studies have shown that a substance (FGF) which is present in the heart, can exist in two versions, a larger (Hi-FGF) and a shorter (Lo-FGF) version. Many previous studies had only studied Lo-FGF2, under the mistaken assumption that Hi-FGF2 is not able to have an effect. In contrast, we have now demonstrated that Hi-FGF2 predominates (in both animals and humans), that it becomes augmented when the heart is diseased, and that it (but not Lo-FGF) can cause both abnormal heart growth and fibrotic changes. We proposed to validate our findings in an experimental model of heart disease, and propose a series of studies aimed at in-depth understanding of how Hi- and Lo-FGF2 are exerting their distinct effects in the heart. These studies can indicate a strategy to neutralize the Hi-FGF2 action, and therefore decrease pathological cardiac changes, in patients