Therapeutic effects of concurrent autologous bone marrow cell infusion and metabolic intervention in ischemia-induced angiogenesis in the hypercholesterolemic mouse hindlimb.
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.
de Nigris
Filomena
F
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.
Williams-Ignarro
Sharon
S
Sica
Vincenzo
V
D'Armiento
Francesco P
FP
Lerman
Lilach O
LO
Byrns
Russell E
RE
Sica
Giacomo
G
Fiorito
Carmela
C
Ignarro
Louis J
LJ
Napoli
Claudio
C
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000235:genetics; D001120:Arginine / Q000494:pharmacology*; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D006614:Hindlimb / Q000098:blood supply; D006937:Hypercholesterolemia / Q000150:complications*; D007511:Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy*; D017078:Laser-Doppler Flowmetry; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D016491:Peripheral Vascular Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy; D012039:Regional Blood Flow; D014182:Transplantation, Autologous; D014463:Ultrasonography
D000975:Antioxidants; D001057:Apolipoproteins E; D009569:Nitric Oxide; D001120:Arginine