title: Role of the renin angiotensin system on bone marrow-derived stem cell function and its impact on skeletal muscle angiogenesis.
abstract: Autologous bone marrow cell (BMC) transplantation has been shown as a potential approach to treat various ischemic diseases. However, under many conditions BMC dysfunction has been reported, leading to poor cell engraftment and a failure of tissue revascularization. We have previously shown that skeletal muscle angiogenesis induced by electrical stimulation (ES) is impaired in the SS/Mcwi rats and that this effect is related to a dysregulation of the renin angiotensin system (RAS) that is normalized by the replacement of chromosome 13 derived from the Brown Norway rat (SS-13(BN)/Mcwi consomic rats). The present study explored bone marrow-derived endothelial cell (BM-EC) function in the SS/Mcwi rat and its impact on skeletal muscle angiogenesis induced by ES. SS/Mcwi rats were randomized to receive BMC from: SS/Mcwi; SS-13(BN)/Mcwi; SS/Mcwi rats infused with saline or ANG II (3 ng kg(-1) min(-1)). BMC were injected in the stimulated tibialis anterior muscle of SS/Mcwi rats. Vessel density was evaluated in unstimulated and stimulated muscles after 7 days of ES. BMC isolated from SS/Mcwi or SS/Mcwi rats infused with saline failed to restore angiogenesis induced by ES. However, BMC isolated from SS-13(BN)/Mcwi and SS/Mcwi rats infused with ANG II effectively restored the angiogenesis response in the SS/Mcwi recipient. Furthermore, ANG II infusion increased the capacity of BM-EC to induce endothelial cell tube formation in vitro and slightly increased VEGF protein expression. This study suggests that dysregulation of the RAS in the SS/Mcwi rat contributes to impaired BM-EC function and could impact the angiogenic therapeutic potential of BMC.
authors.affiliation: Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Micheline M
authors.initials: MM
authors.lastname: de Resende
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Stodola
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Greene
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D004558:Electric Stimulation; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D020303:Rats, Inbred Dahl; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000804:Angiotensin II