Bmi1 and BRG1 drive myocardial repair by regulating cardiac stem cell function in acute rheumatic heart disease.

Abstract

Rheumatic heart disease (RHD) occurs due to the accumulation of complications associated with rheumatic fever, and it results in high morbidity and mortality. The majority of cases of RHD are diagnosed in the chronic stages, when treatment options are limited. A small reservoir of cardiac stem cells is responsible for maintaining cardiac homeostasis and repairing tissue damage. Understanding the role of cardiac stem cells and the various proteins responsible for their functions in different pathological stages of RHD is an important area of investigation. Polycomb complex protein BMI-1 (Bmi1) and transcription activator BRG1 (BRG1) are associated with the maintenance of stemness in various types of stem cells. The present study investigated the role served by Bmi1 and BRG1 in cardiac stem cells during various pathological stages of RHD through immunohistochemistry and western blotting. A rat model of RHD was established via immunization with the Group A Streptococcus M5 protein. The rat was demonstrated to develop acute RHD 2 months after the final immunization, characterized by cardiac inflammation and tissue damage. Chronic RHD was identified 4 months after the final immunization, revealed by cardiac tissue compression and shrinkage. Expression of the cardiac stem cell marker mast/stem cell growth factor receptor kit was identified to be elevated during acute RHD, but downregulated in the chronic stages of RHD. A similar pattern of expression was revealed for Bmi1 and BRG1, indicating that they serve a role in regulating cardiac stem cell proliferation during acute RHD. These results suggest that cardiac stem cells serve a supportive role in the acute, but not chronic, stages of RHD via expression of Bmi1 and BRG1.