TY - JOUR
T1 - Beneficial effects of concurrent autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the mouse hindlimb
AU - Napoli, Claudio
AU - Williams-Ignarro, Sharon
AU - De Nigris, Filomena
AU - De Rosa, Gaetano
AU - Lerman, Lilach O.
AU - Farzati, Bartolomeo
AU - Matarazzo, Angelo
AU - Sica, Giacomo
AU - Botti, Chiara
AU - Fiore, Andrea
AU - Byrns, Russell E.
AU - Sumi, Daigo
AU - Sica, Vincenzo
AU - Ignarro, Louis J.
PY - 2005/11/22
Y1 - 2005/11/22
N2 - 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.
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.
KW - Antioxidants
KW - Ischemic hindlimb
KW - L-arginine
KW - Nitric oxide
KW - Peripheral arterial disease
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U2 - 10.1073/pnas.0508534102
DO - 10.1073/pnas.0508534102
M3 - Article
C2 - 16286655
AN - SCOPUS:28044435059
SN - 0027-8424
VL - 102
SP - 17202
EP - 17206
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 47
ER -