Organosulfur Garlic Compounds Induce Neovasculogenesis in Human Endothelial Progenitor Cells through a Modulation of MicroRNA 221 and the PI3-K/Akt Signaling Pathways

Human endothelial progenitor cells (EPCs) play crucial roles in the prevention of ischemic injury via neovasculogenesis. Frequent garlic consumption is reportedly associated with a low incidence of cardiovascular diseases (CVD). However, the molecular mechanisms by which garlic extracts, including diallyl disulfide (DADS) and diallyl trisulfide (DATS), exert an effect on neovasculogenesis have not been elucidated yet. The current study investigated the effects of these organosulfur compounds on neovasculogenesis by using vascular tube formation assay, Western blotting assay, real-time polymerase chain reaction (RT-PCR), and immunohistochemical (IHC) staining assays in both in vitro and in vivo models. The current study demonstrates that DADS and DATS dose-dependently enhance the neovasculogenesis of human EPCs in vitro. The mechanism of actions included the up-regulation of the c-kit protein, as well as the phosphorylation (i.e., activation) of the Akt and ERK 1/2 signaling molecules in human EPCs. Furthermore, DATS suppressed the expression of microRNA (miR) 221 in vitro. In a mouse xenograft model of neovasculogenesis, DATS consumption induced the formation of new blood vessels at a dosage of 10 mg/kg of body weight/day. It is suggested that garlic consumption enhances neovasculogenesis in human EPCs and thereby probably exerts a preventive effect against ischemic injuries.