Pigment Epithelium-Derived Factor and 34mer Suppress Cardiac Angiogenesis by Up-Regulating Endothelial Notch Activity to Inhibit Tip Cell Formation

Pigment epithelium-derived factor (PEDF) is defined as one of the most potent endogenous anti-angiogenic factors in the human body. However, cellular and molecular mechanisms behind the impact of PEDF and its functional peptides on cardiac angiogenesis are not fully elucidated. In this study, we found that PEDF and 34mer, not 44mer, significantly suppress angiogenesis in the heart and up -regulate Notch signaling in activated endothelial cells (ECs). Moreover, we found that PEDF and 34mer inhibit tip cell formation and suppress cardiac angiogenesis via Notch signaling. This is the first study to identify the involvement of endothelial Notch signaling in PEDF and its functional peptide 34mer mediated suppression of cardiac vascular angiogenesis. Ultimately, this research can provide theoretical basis for clinical trials of new therapeutic targets of the PEDF-derived short peptides in cardiac angiogenesis related diseases.