Role of the renin angiotensin system on bone marrow-derived stem cell function and its impact on skeletal muscle angiogenesis. Physiol Genomics 2010 Aug;42(3):437-44
Date
05/27/2010Pubmed ID
20501694Pubmed Central ID
PMC2929886DOI
10.1152/physiolgenomics.00037.2010Scopus ID
2-s2.0-77955744269 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
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.
Author List
de Resende MM, Stodola TJ, Greene ASMESH terms used to index this publication - Major topics in bold
Angiotensin IIAnimals
Bone Marrow Cells
Bone Marrow Transplantation
Cells, Cultured
Electric Stimulation
Hematopoietic Stem Cells
Humans
Models, Biological
Muscle, Skeletal
Neovascularization, Physiologic
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Renin-Angiotensin System
Vascular Endothelial Growth Factor A