title: Bone marrow-derived cells do not repair endothelium in a mouse model of chronic endothelial cell dysfunction.
abstract: OBJECTIVE
  Bone marrow (BM)-derived endothelial progenitor cells (EPCs) in the circulation replace damaged vascular endothelium. We assessed the hypothesis that a BM transplant from healthy animals would restore normal arterial endothelium and prevent hypertension in young endothelial nitric oxide synthase-deficient (eNOS(-/-)) mice.
  
  
  RESULTS
  Radiation or busulfan-induced BM ablation in eNOS(-/-) mice on day 6, day 14, or day 28 was followed by a BM transplant consisting of enhanced green fluorescent protein positive (EGFP(+)) cells from C57BL/6J mice. Peripheral blood cell chimerism was always greater than 85% at 4 months after BM transplant. Molecular assays of heart, kidney, and liver revealed low-level chimerism in all treatment groups, consistent with residual circulating EGFP(+) blood cells. When aorta, coronary, renal, hepatic, and splenic arteries in BM-transplanted eNOS(-/-) mice were examined by confocal microscopy, there were no EGFP- or eNOS-positive endothelial cells detected in these vessels in any of the treatment groups. Likewise, telemetry did not detect any reduction in blood pressure. Thus, no differences were observed in our measurements using several different treatment protocols.
  
  
  CONCLUSIONS
  We found no evidence for BM-derived EPC renewal of endothelium in this eNOS-deficient mouse model of a chronic vascular disease or in wild-type mice during postnatal growth. Hence, renewal of chronic dysfunctional endothelium and endothelial homeostasis may be dependent on resident vascular progenitor cells.
authors: Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Building 10-CRC, Room 6-3130, Bethesda, MD 20892, USA.
authors: Tashera E
authors: TE
authors: Perry
authors: Minjung
authors: M
authors: Song
authors: Daryl J
authors: DJ
authors: Despres
authors: Soo Mi
authors: SM
authors: Kim
authors: Hong
authors: H
authors: San
authors: Zu-Xi
authors: ZX
authors: Yu
authors: Nalini
authors: N
authors: Raghavachari
authors: Jurgen
authors: J
authors: Schnermann
authors: Richard O
authors: RO
authors: Cannon
authors: Donald
authors: D
authors: Orlic
mesh_terms: D000818:Animals; D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory; D001835:Body Weight; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002908:Chronic Disease; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000201:enzymology / Q000473:pathology / Q000637:transplantation*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006973:Hypertension / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009206:Myocardium / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D033581:Stem Cell Transplantation; D013686:Telemetry; D013997:Time Factors; D018183:Transplantation Chimera
chemical_list: D012333:RNA, Messenger; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004247:DNA; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse