Background Heart failure is a major cause of morbidity and mortality worldwide. The ubiquitously expressed cytokine, transforming growth factor beta-1 (TGFβ1), promotes cardiac fibrosis, an important component of progressive heart failure. Membrane-associated endoglin is a co-receptor for TGFβ1 signaling and has been studied in vascular remodeling and preeclampsia. We hypothesized that reduced endoglin expression may limit cardiac fibrosis in heart failure. Methods and Results We first report that endoglin expression is increased in the left ventricle (LV) of human subjects with heart failure and determined that endoglin is required for TGFβ1 signaling in human cardiac fibroblasts using neutralizing antibodies and a siRNA approach. We further identified that reduced endoglin expression attenuates cardiac fibrosis, preserves LV function, and improves survival in a mouse model of pressure-overload induced heart failure. Prior studies have shown that the extracellular domain of endoglin can be cleaved and released into the circulation as soluble endoglin (sEng), which disrupts TGFβ1 signaling in endothelium. We now demonstrate that sEng limits TGFβ1 signaling and Type I collagen synthesis in cardiac fibroblasts and further show that sEng treatment attenuates cardiac fibrosis in an in vivo model of heart failure. Conclusions Our results identify endoglin as a critical component of TGFβ1 signaling in the cardiac fibroblast and that targeting endoglin attenuates cardiac fibrosis, thereby providing a potentially novel therapeutic approach for individuals with heart failure.

Forty-one zoological gardens in seven European countries were visited to investigate activity level in captive environments for great apes. Forty-three groups of gorillas and 68 groups of orangutans were observed. The seven factors quantified for each of the environments were size of the enclosure, usable surface area, frequency of feeding, number of animals, and number of objects (stationary, temporary, and movable). Activity level of each group was measured by instantaneous scan sampling for one hour on two consecutive days. For both species, the factors most highly related to activity level were number of animals, and stationary, temporary, and movable objects. The usefulness o f these variables for predicting group activity level was different for the two species, however. Factors important for gorillas were stationary and temporary objects, while stationary and movable objects were significant for orangutans. These findings suggest that objects within environments may be more important for captive apes than the size or construction of the enclosure. Also, the types of objects that need to be included in environments may be related to the natural behavior of the individual species.