Recombinant Human Interleukin-11 Treatment Enhances Collateral Vessel Growth After Femoral Artery Ligation

被引:16
作者
Aitsebaomo, Julius [1 ,2 ,3 ]
Srivastava, Siddharth [1 ]
Zhang, Hua [1 ,4 ]
Jha, Sushmita [4 ,6 ]
Wang, Zhongjing [1 ]
Winnik, Stephan [7 ]
Veleva, Anka N. [5 ]
Pi, Xinchun [1 ]
Lockyer, Pamela [1 ]
Faber, James E. [1 ,4 ]
Patterson, Cam [1 ,2 ,3 ]
机构
[1] N Carolina State Univ, McAllister Heart Inst, Raleigh, NC 27695 USA
[2] N Carolina State Univ, Dept Med, Raleigh, NC 27695 USA
[3] N Carolina State Univ, Div Cardiol, Raleigh, NC 27695 USA
[4] N Carolina State Univ, Dept Cell & Mol Physiol, Raleigh, NC 27695 USA
[5] N Carolina State Univ, Dept Chem & Biomed Engn, Raleigh, NC 27695 USA
[6] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
[7] Univ Freiburg, Dept Med, D-7800 Freiburg, Germany
基金
美国国家卫生研究院;
关键词
blood flow; ischemia; peripheral arterial disease; peripheral vasculature; reperfusion; ENDOTHELIAL PROGENITOR CELLS; CIRCULATING CD34-POSITIVE CELLS; BONE-MARROW; THERAPEUTIC ANGIOGENESIS; AUTOLOGOUS TRANSPLANTATION; SIGNAL TRANSDUCER; CANCER; MOBILIZATION; ACTIVATION; EXPRESSION;
D O I
10.1161/ATVBAHA.110.216986
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective-To investigate the role of recombinant human interleukin-11 (rhIL-11) on in vivo mobilization of CD34(+)/vascular endothelial growth factor receptor (VEGFR) 2(+) mononuclear cells and collateral vessel remodeling in a mouse model of hindlimb ischemia. Methods and Results-We observed that treatment of Sv129 mice with continuous infusion of 200-mu g/kg rhIL-11 per day led to in vivo mobilization of CD34(+)/VEGFR2(+) cells that peaked at 72 hours. Sv129 mice pretreated with rhIL-11 for 72 hours before femoral artery ligation showed a 3-fold increase in plantar vessel perfusion, leading to faster blood flow recovery; and a 20-fold increase in circulating CD34(+)/VEGFR2(+) cells after 8 days of rhIL-11 treatment. Histologically, experimental mice had a 3-fold increase in collateral vessel luminal diameter after 21 days of rhIL-11 treatment and a 4.4-fold influx of perivascular CD34(+)/VEGFR2(+) cells after 8 days of therapy. Functionally, rhIL-11-treated mice showed better hindlimb appearance and use scores when compared with syngeneic mice treated with PBS under the same experimental conditions. Conclusion-These novel findings show that rhIL-11 promotes in vivo mobilization of CD34(+)/VEGFR2(+) mononuclear cells, enhances collateral vessel growth, and increases recovery of perfusion after femoral artery ligation. Thus, rhIL-11 has a promising role for development as an adjunctive treatment of patients with peripheral vascular disease. (Arterioscler Thromb Vasc Biol. 2011;31:306-312.)
引用
收藏
页码:306 / 312
页数:7
相关论文
共 35 条
[1]   Cell Therapy in Peripheral Arterial Disease [J].
Al Mheid, Ibhar ;
Quyyumi, Arshed A. .
ANGIOLOGY, 2008, 59 (06) :705-716
[2]  
Arain FA, 2008, MAYO CLIN PROC, V83, P944, DOI 10.4065/83.8.944
[3]   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
[4]  
Buschmann I, 1999, NEWS PHYSIOL SCI, V14, P121
[5]   Dopamine regulates endothelial progenitor cell mobilization from mouse bone marrow in tumor vascularization [J].
Chakroborty, Debanjan ;
Chowdhury, Uttio Roy ;
Sarkar, Chandrani ;
Baral, Rathindranath ;
Dasgupta, Partha Sarathi ;
Basu, Sujit .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (04) :1380-1389
[6]   Catecholamines augment collateral vessel growth and angiogenesis in hindlimb ischemia [J].
Chalothorn, D ;
Zhang, H ;
Clayton, JA ;
Thomas, SA ;
Faber, JE .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2005, 289 (02) :H947-H959
[7]   Collateral density, remodeling, and VEGF-A expression differ widely between mouse strains [J].
Chalothorn, Dan ;
Clayton, Jason A. ;
Zhang, Hua ;
Pomp, Daniel ;
Faber, James E. .
PHYSIOLOGICAL GENOMICS, 2007, 30 (02) :179-191
[8]   Vascular Endothelial Growth Factor-A Specifies Formation of Native Collaterals and Regulates Collateral Growth in Ischemia [J].
Clayton, Jason A. ;
Chalothorn, Dan ;
Faber, James E. .
CIRCULATION RESEARCH, 2008, 103 (09) :1027-U275
[9]  
DU XX, 1994, BLOOD, V83, P2023
[10]   Interleukin-11: Review of molecular, cell biology, and clinical use [J].
Du, XX ;
Williams, DA .
BLOOD, 1997, 89 (11) :3897-3908