PMID- 16875745 OWN - NLM STAT- MEDLINE DCOM- 20070507 LR - 20161124 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 117 IP - 2 DP - 2007 Apr 25 TI - Therapeutic effects of concurrent autologous bone marrow cell infusion and metabolic intervention in ischemia-induced angiogenesis in the hypercholesterolemic mouse hindlimb. PG - 238-43 AB - Lower-limb ischemia is a major health problem especially when associated to hypercholesterolemia. Because of the absence of effective treatment in the advanced stages of the disease, amputation is undertaken to alleviate unbearable symptoms. Since tissue ischemia and hypercholesterolemia are associated with an overwhelming generation of oxygen radicals, metabolic intervention with antioxidants and l-arginine can induce beneficial effects beyond those achieved by a novel therapeutic approach represented by the use of autologous bone marrow cells (BMCs). The protective effect of BMCs and vascular protection by metabolic cotreatment (1.0% vitamin E added to the chow, 0.05% vitamin C and 6% l-arginine added to the drinking water) were examined in ischemia-induced angiogenesis in the hypercholesterolemic mouse hindlimb. Intravenous BMC therapy improved blood flow and increased capillary densities. 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. 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 80138, Italy. FAU - Williams-Ignarro, Sharon AU - Williams-Ignarro S FAU - Sica, Vincenzo AU - Sica V FAU - D'Armiento, Francesco P AU - D'Armiento FP FAU - Lerman, Lilach O AU - Lerman LO FAU - Byrns, Russell E AU - Byrns RE FAU - Sica, Giacomo AU - Sica G FAU - Fiorito, Carmela AU - Fiorito C 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 DEP - 20060727 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 0 (Antioxidants) RN - 0 (Apolipoproteins E) RN - 31C4KY9ESH (Nitric Oxide) RN - 94ZLA3W45F (Arginine) SB - IM MH - Animals MH - Antioxidants/*pharmacology MH - Apolipoproteins E/genetics MH - Arginine/*pharmacology MH - *Bone Marrow Transplantation MH - Combined Modality Therapy MH - Disease Models, Animal MH - Hindlimb/blood supply MH - Hypercholesterolemia/*complications MH - Ischemia/diagnostic imaging/*drug therapy MH - Laser-Doppler Flowmetry MH - Macrophages/metabolism MH - Male MH - Mice MH - Mice, Knockout MH - Neovascularization, Physiologic/drug effects MH - Nitric Oxide/metabolism MH - Oxidative Stress/drug effects MH - Peripheral Vascular Diseases/diagnostic imaging/drug therapy MH - Regional Blood Flow MH - Transplantation, Autologous MH - Ultrasonography EDAT- 2006/08/01 09:00 MHDA- 2007/05/08 09:00 CRDT- 2006/08/01 09:00 PHST- 2006/02/08 00:00 [received] PHST- 2006/05/03 00:00 [accepted] PHST- 2006/08/01 09:00 [pubmed] PHST- 2007/05/08 09:00 [medline] PHST- 2006/08/01 09:00 [entrez] AID - S0167-5273(06)00554-7 [pii] AID - 10.1016/j.ijcard.2006.05.020 [doi] PST - ppublish SO - Int J Cardiol. 2007 Apr 25;117(2):238-43. doi: 10.1016/j.ijcard.2006.05.020. Epub 2006 Jul 27.