SummaryThe clinical goal of cell-based treatment for chronic heart failure is to coordinately reconstitute the cardiomyocytes and associated circulation environment including coronary resistance arteries, arterioles, and capillary profiles.1) This goal can be possibly achieved by implementing multipotent adult stem cells. However, it remains a challenge to modify the capillary network in the decompensated heart. A mechanical stress model was used in this study to mimic the hemodynamic and hormonal states of the decompensated heart in vitro. The angiogenesis role of endothelial progenitor cells (EPCs) under stress has been well-recognized in vascular repair. We investigated the molecular mechanisms of EPCs in this model. We found that expression of vascular endothelial growth factor (VEGF) in EPCs was significantly decreased by mechanical stress, and this effect was accompanied by a decrease in angiogenesis in vitro. Interestingly, the defective angiogenesis can be reversed by upregulating the membrane VEGF receptor (VEGFR) endocytosis. An atypical protein kinase C (aPKC) inhibitor can promote the VEGFR internalization in EPCs and enhance the formation of vascular networks. Thus, the upregulation of VEGFR endocytosis in EPCs could be a potential therapy for the cell-based treatment of chronic heart failure by enhancing the cardiomyocytes. (Int Heart J 2016; 57: 356-362) Key words: Cell-based treatment, Capillary network I n the last decade, several types of cells have been utilized in cell-based therapies to treat acute myocardial infarction and chronic heart failure (CHF). Endothelial progenitor cells (EPCs) are a useful cell type that has been tested experimentally in patients with encouraging results.2-6) Kocher, et al 7) infused freshly isolated human EPCs into a nude rat model of myocardial ischemia and observed preservation of left ventricular (LV) function and inhibition of cardiac apoptosis. More than 10 clinical trials [4][5][6][8][9][10][11][12][13][14] have been performed to elucidate the therapeutic effects of EPCs. These studies have provided information regarding the feasibility of using EPCsbased therapy to promote vasculogenesis. Despite these promising results, the search for a means to reverse the negative remodeling associated with CHF remains a concern. 15) This search is complicated by numerous factors that influence the growth and behavior of harvested cells. These factors include the age of the organ, the pathological state, and the severity of the cardiac disease. 16,17) Additionally, insufficient oxygen supply provided by the existing capillary network further complicates the extent of the therapeutic benefit provided by stem/progenitor cells.
Editorial p.268Currently, the means of modifying the regeneration and integrity of the capillary network in the failing and hypertrophied decompensated heart are limited clinically, and the underlying mechanism remains unclear. The viability, proliferation, migration, and angiogenesis of EPCs are four critical determinants of revascularization in...