Endothelial to Mesenchymal Transition and the Reverse Contributes to Heart Failure and Recovery Thereafter

Abstract

Introduction Previous studies have demonstrated Endothelial to Mesenchymal Transition (EndMT) in heart failure (HF) and it likely contributes to cardiac fibrosis. The reverse phenomenon of Mesenchymal to Endothelial Transition (MET) has not been well described in the setting of reversal of fibrosis. We aim to evaluate the occurrence of such cell transitions in mouse model of non-ischemic HF and recovery from HF. Hypothesis Endothelial to Mesenhcymal transitions contribute to heart failure while the reverse contributes to the recovery from HF. Methods HF is induced in C57BL/6 mice by exposure to water containing L-NAME and NaCL and implantation of an osmotic pump delivering Angiotensin II, which induces HF in 5 weeks. At 5 weeks the pump runs out of Angiotensin II and the water is changed back to normal water. Previous observations have shown a reduction of heart failure markers over an additional 14 weeks (19 week total). In the current experiment we decided to focus during the maximum reversal of fibrosis based on previous data and hence stopped the recovery phase at Week 9. Dual immunohistochemical staining was applied using antibodies to α-SMA (fibroblast cell marker) and CD31 (endothelial cell marker) to identify cells under transition. Results In line with previous observations the HF phenotype peaks at week 5 and reverses through week 9. (Figure 1B). Dual staining cells have a double peak during Week 3 and Week7 suggesting cell transitions to contribute to both heart failure and recovery. Conclusions While endothelial to mesenchymal transition contributes to the fibrotic state of heart failure, the reverse transitions could be playing a role in the remodeling of the heart in recovery.