title: Bone marrow AT1 augments neointima formation by promoting mobilization of smooth muscle progenitors via platelet-derived SDF-1{alpha}.
abstract: OBJECTIVE
  Bone marrow (BM)-derived endothelial progenitor cells (EPCs) and vascular smooth muscle progenitor cells (VPCs) contribute to neointima formation, whereas the angiotensin II (Ang II) type 1 receptor (AT(1))-mediated action on BM-derived progenitors remains undefined.
  
  
  RESULTS
  A wire-induced vascular injury was performed in the femoral artery of BM-chimeric mice whose BM was repopulated with AT(1)-deficient (BM-Agtr1(-/-)) or wild-type (BM-Agtr1(+/+)) cells. Neointima formation was profoundly reduced by 38% in BM-Agtr1(-/-) mice. Although the number of circulating EPCs (Sca-1(+)Flk-1(+)) and extent of reendothelialization did not differ between the 2 groups, the numbers of both circulating VPCs (c-Kit(-)Sca-1(+)Lin(-)) and tissue VPCs (Sca-1(+)CD31(-)) incorporated into neointima were markedly decreased in BM-Agtr1(-/-) mice. The accumulation of aggregated platelets and their content of stromal cell-derived factor-1alpha (SDF-1alpha) were significantly reduced in BM-Agtr1(-/-) mice, accompanied by a decrease in the serum level of SDF-1alpha. Thrombin-induced platelets aggregation was dose-dependently inhibited (45% at 0.1 IU/mL, P<0.05) in Agtr1(-/-) platelets compared with Agtr1(+/+) platelets, accompanied by the reduced expression and release of SDF-1alpha.
  
  
  CONCLUSIONS
  The BM-AT(1) receptor promotes neointima formation by regulating the mobilization and homing of BM-derived VPCs in a platelet-derived SDF-1alpha-dependent manner without affecting EPC-mediated reendothelialization.
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University School of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566 Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yokoi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsubakimoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawahito
authors.forename: Sou
authors.initials: S
authors.lastname: Kishida
authors.forename: Taku
authors.initials: T
authors.lastname: Kato
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsui
authors.forename: Hideyo
authors.initials: H
authors.lastname: Hirai
authors.forename: Eishi
authors.initials: E
authors.lastname: Ashihara
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Iwai
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Kouji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Tomosaburo
authors.initials: T
authors.lastname: Takahashi
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Okigaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsubara
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D001853:Bone Marrow / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D054377:Chemokine CXCL12 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D010974:Platelet Aggregation / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D017539:Tunica Intima / Q000166:cytology / Q000378:metabolism
chemical_list: D000906:Antibodies; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D044140:Receptor, Angiotensin, Type 1