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Therapeutic effects of concurrent autologous bone marrow cell infusion and metabolic intervention in ischemia-induced angiogenesis in the hypercholesterolemic mouse hindlimb.

Abstract
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.
AuthorsFilomena de Nigris, Sharon Williams-Ignarro, Vincenzo Sica, Francesco P D'Armiento, Lilach O Lerman, Russell E Byrns, Giacomo Sica, Carmela Fiorito, Louis J Ignarro, Claudio Napoli
JournalInternational journal of cardiology (Int J Cardiol) Vol. 117 Issue 2 Pg. 238-43 (Apr 25 2007) ISSN: 1874-1754 [Electronic] Netherlands
PMID16875745 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antioxidants
  • Apolipoproteins E
  • Nitric Oxide
  • Arginine
Topics
  • Animals
  • Antioxidants (pharmacology)
  • Apolipoproteins E (genetics)
  • Arginine (pharmacology)
  • Bone Marrow Transplantation
  • Combined Modality Therapy
  • Disease Models, Animal
  • Hindlimb (blood supply)
  • Hypercholesterolemia (complications)
  • Ischemia (diagnostic imaging, drug therapy)
  • Laser-Doppler Flowmetry
  • Macrophages (metabolism)
  • Male
  • Mice
  • Mice, Knockout
  • Neovascularization, Physiologic (drug effects)
  • Nitric Oxide (metabolism)
  • Oxidative Stress (drug effects)
  • Peripheral Vascular Diseases (diagnostic imaging, drug therapy)
  • Regional Blood Flow
  • Transplantation, Autologous
  • Ultrasonography

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