Role of MLL3 in regulating cardiac stem cells following cardiac cachexia

Cardiac cachexia is a form of serious illness that results with terminal stage of heart failure. It is associated with unreasonable weight loss and muscle loss with poor prognosis. Cardiac stem cells play a major role in repairing, damaged cardiac tissue and they are regulated by different mechanisms. In the present study, we investigated the role of MLL3 in regulating cardiac stem cells following cardiac cachexia.

To effectively study the cardiac cachexia, we established a Dahl rat model that produces symptoms similar to cachexia. Using histology, we analyzed the acute and chronic stage of cardiac cachexia. Immunohistochemistry and Western blotting were used to analyze the expression of MLL3 and Oct-4.

The rat develops an acute form of cachexia after 2 months of fed with high-salt (8% NaCl) diet, which is characterized by inflammation and tissue damage that are observed through the histological sectioning. The chronic cardiac cachexia developed after 5 months of high-salt diet and histologically it shows tissue loss. At the molecular level the stem cell marker, Oct-4, shows elevated expression at acute stage, but down regulated latter in the chronic stage of cardiac cachexia. Also, MLL3 shows a similar pattern of upregulated expression in acute stage of cachexia, but significantly down regulated in the chronic stage of cachexia that implies their role in regulating the cardiac stem cell and their proliferation.

Our results show that the cardiac stem cells in association with MLL3 support in maintaining homeostatic after initial pathological stages of cachexia but not in the chronic stage of cachexia.