Endothelial characteristics of cardiac stem cell antigen-1 expressing cells and their relevance to right ventricular adaptation

A growing body of evidence suggest that the stem cell antigen-1 expressing (Sca-1⁺) cells in the heart may be the cardiac endothelial stem/progenitor cells. Their endothelial cell (EC) functions, and their role in right ventricle (RV) physiology and pathophysiology of right heart failure (RHF) remains poorly defined. This study investigated EC characteristics of rat cardiac Sca-1⁺ cells, assessed spatial distribution and studied changes in Sca-1⁺ cells during RV remodelling in monocrotaline (MCT) model of pulmonary hypertension and RV remodeling. First, flow-cytometry analysis of adult male and female Sprague Dawley (SD) and Fischer CDF rat heart cells was performed, and we observed that the majority of Sca-1⁺ cells also expressed CD31, an EC marker. Furthermore, Sca-1⁺ cells showed acetylated low-density lipoprotein (ac-LDL) uptake and lectin binding similar to CD31⁺ cells from the same heart. The Sca-1⁺ cells also demonstrated network formation when plated on Matrigel. In the MCT treated rats, we observed increase in RV hypertrophy that correlated with the reduction in the abundance of Sca-1⁺CD31⁺ cells in the RV. Together, the cardiac Sca-1⁺ cells in the heart are endothelial stem/progenitor-like cells. These cells have higher abundance in the RV and may play a role in RV adaptation.