title: Organosulfur garlic compounds induce neovasculogenesis in human endothelial progenitor cells through a modulation of MicroRNA 221 and the PI3-K/Akt signaling pathways.
abstract: 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.
authors.affiliation: Department of Food Science and Biotechnology and ‡Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: En-Pei Isabel
authors.initials: EP
authors.lastname: Chiang
authors.forename: Shao-Chih
authors.initials: SC
authors.lastname: Chiu
authors.forename: Man-Hui
authors.initials: MH
authors.lastname: Pai
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Wang
authors.forename: Fu-Yu
authors.initials: FY
authors.lastname: Wang
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.forename: Feng-Yao
authors.initials: FY
authors.lastname: Tang
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004220:Disulfides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology* / Q000637:transplantation; D005260:Female; D005737:Garlic / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000187:drug effects* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D013440:Sulfides / Q000494:pharmacology*
chemical_list: D000498:Allyl Compounds; D004220:Disulfides; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D013440:Sulfides; C525709:MIR221, human; C546122:MIRN221 microRNA, mouse; C042577:diallyl trisulfide; C028009:diallyl disulfide