Beneficial effects of concurrent autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the mouse hindlimb

被引:58
作者
Napoli, C
Williams-Ignarro, S
de Nigris, F
de Rosa, G
Lerman, LO
Farzati, B
Matarazzo, A
Sica, G
Botti, C
Fiore, A
Byrns, RE
Sumi, D
Sica, V
Ignarro, LJ [1 ]
机构
[1] Univ Naples 2, Dept Gen Pathol, Div Clin Pathol, I-80138 Naples, Italy
[2] Univ Naples 2, Excellence Res Ctr Cardiovasc Dis, Sch Med, I-80138 Naples, Italy
[3] Boston Univ, Whitaker Cardiovasc Inst, Boston, MA 02118 USA
[4] Univ Naples Federico II, Dept Biomorphol Sci, I-80131 Naples, Italy
[5] Mayo Clin & Mayo Fdn, Coll Med, Div Nephrol & Hypertens, Rochester, MN 55905 USA
[6] Univ Calif Los Angeles, Dept Mol Pharmacol, David Geffen Sch Med, Los Angeles, CA 90095 USA
[7] Univ Calif Los Angeles, Div Anesthesiol, Los Angeles, CA 90095 USA
关键词
antioxidants; ischemic hindlimb; L-arginine; peripheral arterial disease; nitric oxide;
D O I
10.1073/pnas.0508534102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:17202 / 17206
页数:5
相关论文
共 39 条
[1]  
Aronow Wilbert S, 2005, Cardiol Rev, V13, P61, DOI 10.1097/01.crd.0000126082.86717.12
[2]   Monocyte activation in angiogenesis and collateral growth in the rabbit hindlimb [J].
Arras, M ;
Ito, WD ;
Scholz, D ;
Winkler, B ;
Schaper, J ;
Schaper, W .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (01) :40-50
[3]   Isolation of putative progenitor endothelial cells for angiogenesis [J].
Asahara, T ;
Murohara, T ;
Sullivan, A ;
Silver, M ;
vanderZee, R ;
Li, T ;
Witzenbichler, B ;
Schatteman, G ;
Isner, JM .
SCIENCE, 1997, 275 (5302) :964-967
[4]  
Baumgartner I, 2000, Curr Cardiol Rep, V2, P24
[5]   New concepts in reactive oxygen species and cardiovascular reperfusion physiology [J].
Becker, LB .
CARDIOVASCULAR RESEARCH, 2004, 61 (03) :461-470
[6]  
Boak L., 2004, Current Vascular Pharmacology, V2, P45, DOI 10.2174/1570161043476546
[7]   Update on therapeutic neovascularization [J].
Cao, YH ;
Hong, A ;
Schulten, H ;
Post, MJ .
CARDIOVASCULAR RESEARCH, 2005, 65 (03) :639-648
[8]   Augmentation of therapeutic angiogenesis using genetically modified human endothelial progenitor cells with altered glycogen synthase kinase-3β activity [J].
Choi, JH ;
Hur, J ;
Yoon, CH ;
Kim, JH ;
Lee, CS ;
Youn, SW ;
Oh, IY ;
Skurk, C ;
Murohara, T ;
Park, YB ;
Walsh, K ;
Kim, HS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (47) :49430-49438
[9]  
Committee on Care and Use of Laboratory Animals, 1985, DHHS PUBL, V85-23
[10]   Atherogenesis and the arginine hypothesis. [J].
Cooke J.P. ;
Oka R.K. .
Current Atherosclerosis Reports, 2001, 3 (3) :252-259