title: Maturation of blood vessels by haematopoietic stem cells and progenitor cells: involvement of apelin/APJ and angiopoietin/Tie2 interactions in vessel caliber size regulation.
abstract: Apelin is a recently-isolated bioactive peptide from bovine gastric extract. The gene encodes a protein of 77 amino acids, which can generate two active polypeptides, long (42-77) and short (65-77). Both peptides ligate and activate APJ, a G protein-coupled receptor expressed in the cardiovascular and central nervous systems. Although an essential role for the apelin/APJ system in blood vessel formation has been reported in Xenopus, its precise function in mammals is unclear. Blood vessel tube formation is accomplished by two main mechanisms: 1) single cell hollowing, in which a lumen forms within the cytoplasm of a single endothelial cell (EC), and 2) cord hollowing in which a luminal cavity is created de novo between ECs in a thin cylindrical cord. Molecular control of either single cell or cord hollowing has not been precisely determined. Angiopoietin-1 (Ang1) has been reported to induce enlargement of blood vessels. Apelin is produced from ECs upon activation of Tie2, a cognate receptor of Ang1, expressed on ECs. It has been suggested that apelin induces cord hollowing by promoting proliferation and aggregation/assembly of ECs. During angiogenesis, haematopoietic stem cells (HSCs) and progenitor cells (HPCs) are frequently observed in the perivascular region. They produce Ang1 and induce migration of ECs, resulting in a fine vascular network. Moreover, HSCs/HPCs can induce apelin production from ECs. Therefore, this review article posits that HSCs/HPCs regulate caliber size of blood vessels via apelin/APJ and Angiopoietin/Tie2 interactions.
authors.affiliation: Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita-shi, Osaka 565-0871, Japan. ntakaku@biken.osaka-u.ac.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kidoya
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism*; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D001808:Blood Vessels / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D002417:Cattle; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009024:Morphogenesis / Q000502:physiology; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D042787:Receptor, TIE-2 / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D014981:Xenopus
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D042683:Angiopoietin-1; D000073861:Apelin; D000075244:Apelin Receptors; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D042787:Receptor, TIE-2