PMID- 18049311
OWN - NLM
STAT- MEDLINE
DCOM- 20080205
LR  - 20220316
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 50
IP  - 4
DP  - 2007 Oct
TI  - Therapeutic effects of autologous bone marrow cells and metabolic intervention in 
      the ischemic hindlimb of spontaneously hypertensive rats involve reduced cell 
      senescence and CXCR4/Akt/eNOS pathways.
PG  - 424-33
AB  - Peripheral arterial disease (PAD) is a major health problem, especially when 
      associated with severe hypertension. Administration of autologous bone marrow 
      cells (BMCs) is emerging as a novel intervention to induce neoangiogenesis in 
      ischemic limb models and in patients with PAD. This study evaluates the 
      neovascularization capacity of BMCs alone or in combination with metabolic 
      cotreatment (0.8% vitamin E, 0.05% vitamin C, and 5% of L-arginine) in a rat 
      model of ischemic hindlimbs of spontaneously hypertensive rats (SHR) and 
      normotensive Wistar-Kyoto rats (WKY). Molecular mechanisms were investigated in 
      bone marrow-derived endothelial progenitor cells (BM-EPC) derived from rats. BMC 
      therapy increased blood flow and capillary densities and Ki67 proliferative 
      marker, and it decreased interstitial fibrosis. These effects were amplified by 
      metabolic cotreatment, an intervention that induces vascular protection at least 
      partly through the nitric oxide (NO)/endothelial nitric oxide synthase (eNOS) 
      pathway, reduction of systemic oxidative stress, and macrophage activation. In 
      addition, BMC therapy alone and, more consistently, in combination with metabolic 
      treatment, ameliorated BM-EPC functional activity via decreased cellular 
      senescence and improved homing capacity by increasing CXCR4-expression levels. 
      These data suggest potential therapeutic effects of autologous BMCs and metabolic 
      treatment in hypertensive PAD patients.
FAU - de Nigris, Filomena
AU  - de Nigris F
AD  - Department of General Pathology, Division of Clinical Pathology and Excellence 
      Research Center on Cardiovascular Diseases, 1st School of Medicine, II University 
      of Naples, Naples, Italy.
FAU - Balestrieri, Maria Luisa
AU  - Balestrieri ML
FAU - Williams-Ignarro, Sharon
AU  - Williams-Ignarro S
FAU - D'Armiento, Francesco P
AU  - D'Armiento FP
FAU - Lerman, Lilach O
AU  - Lerman LO
FAU - Byrns, Russell
AU  - Byrns R
FAU - Crimi, Ettore
AU  - Crimi E
FAU - Palagiano, Antonio
AU  - Palagiano A
FAU - Fatigati, Gennaro
AU  - Fatigati G
FAU - Ignarro, Louis J
AU  - Ignarro LJ
FAU - Napoli, Claudio
AU  - Napoli C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Antioxidants)
RN  - 0 (Cxcr4 protein, rat)
RN  - 0 (Receptors, CXCR4)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Antioxidants/therapeutic use
MH  - Apoptosis/drug effects
MH  - Arginine/therapeutic use
MH  - Arteries/drug effects/metabolism/physiopathology
MH  - Bone Marrow Transplantation/*methods
MH  - Capillaries/pathology
MH  - Cell Proliferation/drug effects
MH  - Cellular Senescence/drug effects
MH  - Endothelial Cells/cytology/metabolism
MH  - Hindlimb/*blood supply/drug effects/physiopathology
MH  - Ischemia/metabolism/physiopathology/*therapy
MH  - Leukocytes/pathology
MH  - Male
MH  - Mesenchymal Stem Cells/cytology/drug effects/*metabolism
MH  - Muscle, Skeletal/blood supply/pathology
MH  - Nitric Oxide/blood
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Nitric Oxide Synthase Type III
MH  - Oxidative Stress/drug effects
MH  - Peripheral Vascular Diseases/therapy
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Receptors, CXCR4/metabolism
MH  - Regional Blood Flow
EDAT- 2007/12/01 09:00
MHDA- 2008/02/06 09:00
CRDT- 2007/12/01 09:00
PHST- 2007/12/01 09:00 [pubmed]
PHST- 2008/02/06 09:00 [medline]
PHST- 2007/12/01 09:00 [entrez]
AID - 00005344-200710000-00011 [pii]
AID - 10.1097/FJC.0b013e31812564e4 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2007 Oct;50(4):424-33. doi: 10.1097/FJC.0b013e31812564e4.