PMID- 16286655 OWN - NLM STAT- MEDLINE DCOM- 20060112 LR - 20181113 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 102 IP - 47 DP - 2005 Nov 22 TI - Beneficial effects of concurrent autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the mouse hindlimb. PG - 17202-6 AB - Lower-limb ischemia is a major health problem. Because of the absence of effective treatment in the advanced stages of the disease, amputation is undertaken to alleviate unbearable symptoms. Novel therapeutic approaches include the intramuscular use of autologous bone marrow cells (BMCs). Because tissue ischemia is associated with an overwhelming generation of oxygen radicals and negative effects due to perturbed shear-stress, metabolic intervention with antioxidants and l-arginine could potentially induce beneficial effects beyond those achieved by BMCs. The protective effect of autologous BMCs and vascular protection by metabolic cotreatment (1.0% vitamin E added to the chow and 0.05% vitamin C and 6% l-arginine added to the drinking water) were examined in ischemia-induced angiogenesis in the mouse hindlimb, a model of extensive acute peripheral arterial occlusion. i.v. BMC therapy improved blood flow and increased capillary densities and expression of Ki-67, a proliferation-associated protein. This beneficial effect was amplified by metabolic cotreatment, an intervention inducing vascular protection, at least in part, through the nitric oxide pathway, reduction of systemic oxidative stress, and macrophage activation. Therefore, although a cautious approach is mandatory when experimental findings are extended to human diseases, autologous BMCs together with metabolic intervention could be an effective clinical treatment for peripheral arterial disease. FAU - Napoli, Claudio AU - Napoli C AD - Department of General Pathology, Division of Clinical Pathology and Excellence Research Center on Cardiovascular Diseases, School of Medicine, Second University of Naples, Naples 80138, Italy. claunap@tin.it FAU - Williams-Ignarro, Sharon AU - Williams-Ignarro S FAU - de Nigris, Filomena AU - de Nigris F FAU - de Rosa, Gaetano AU - de Rosa G FAU - Lerman, Lilach O AU - Lerman LO FAU - Farzati, Bartolomeo AU - Farzati B FAU - Matarazzo, Angelo AU - Matarazzo A FAU - Sica, Giacomo AU - Sica G FAU - Botti, Chiara AU - Botti C FAU - Fiore, Andrea AU - Fiore A FAU - Byrns, Russell E AU - Byrns RE FAU - Sumi, Daigo AU - Sumi D FAU - Sica, Vincenzo AU - Sica V FAU - Ignarro, Louis J AU - Ignarro LJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20051114 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Antioxidants) RN - 0 (Nitrates) RN - 0 (Nitrites) RN - 94ZLA3W45F (Arginine) SB - IM MH - Animals MH - Antioxidants/*administration & dosage MH - Arginine/administration & dosage MH - *Bone Marrow Transplantation/pathology MH - Disease Models, Animal MH - Fluorescent Antibody Technique MH - Hindlimb/*blood supply MH - Ischemia/*metabolism/pathology/physiopathology/*surgery MH - Mice MH - Neovascularization, Pathologic/*metabolism/pathology/physiopathology/*surgery MH - Nitrates/blood MH - Nitrites/blood MH - *Oxidative Stress/drug effects MH - Transplantation, Autologous/pathology PMC - PMC1288005 EDAT- 2005/11/16 09:00 MHDA- 2006/01/13 09:00 PMCR- 2006/05/22 CRDT- 2005/11/16 09:00 PHST- 2005/11/16 09:00 [pubmed] PHST- 2006/01/13 09:00 [medline] PHST- 2005/11/16 09:00 [entrez] PHST- 2006/05/22 00:00 [pmc-release] AID - 0508534102 [pii] AID - 17202 [pii] AID - 10.1073/pnas.0508534102 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17202-6. doi: 10.1073/pnas.0508534102. Epub 2005 Nov 14.