Angiopoietin-1 and vascular endothelial growth factor induce expression of inflammatory cytokines before angiogenesis

被引:62
作者
Aplin, Alfred C.
Gelati, Maurizio
Fogel, Eric
Carnevale, Edvige
Nicosia, Roberto F.
机构
[1] VA Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Lab S113, Seattle, WA 98108 USA
[2] Carlo Besta Inst, Lab Neurobiol & Neuroregenerat Med, Milan, Italy
[3] Univ Washington, Dept Pathol, Seattle, WA 98195 USA
关键词
aorta; oligonucleotide microarray; gene profiling;
D O I
10.1152/physiolgenomics.00048.2006
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The purpose of this study was to identify novel transcriptional events occurring in the aortic wall before angiogenesis. We used a defined tissue culture system that takes advantage of the capacity of rat aortic rings to generate neovessels ex vivo in response to angiogenic factor stimulation. Total RNA isolated from aortic rings 18 h posttreatment with angiopoietin (Ang)-1 or vascular endothelial growth factor (VEGF) was used to probe oligonucleotide microarrays. Many genes were up- or downregulated by either Ang-1 or VEGF, with a subset being affected by treatment with both growth factors. Grouping of genes by biological function revealed that Ang-1 and VEGF both upregulated a host of immune-related genes including many inflammatory cytokines. A mixture of the Ang-1- and VEGF-induced cytokines stimulated the spontaneous angiogenic response of aortic rings and was synergistic with a low dose of recombinant VEGF. This effect was associated with enhanced recruitment of adventitial macrophages and dendritic cells in the angiogenic outgrowths. Thus Ang-1 and VEGF activate the innate immune system of the vessel wall, stimulating the production of proangiogenic inflammatory cytokines before the emergence of neovessels. This hitherto unreported feature of the angiogenic response might represent an important early component of the cellular and molecular cascade responsible for the angiogenic response of the aortic wall.
引用
收藏
页码:20 / 28
页数:9
相关论文
共 59 条
[1]   cDNA microarray analysis of the gene expression profile of VEGF-activated human umbilical vein endothelial cells [J].
Abe M. ;
Sato Y. .
Angiogenesis, 2001, 4 (4) :289-298
[2]  
Adams NC, 2002, DEVELOPMENT, V129, P965
[3]  
Afuwape AO, 2002, HISTOL HISTOPATHOL, V17, P961, DOI 10.14670/HH-17.961
[4]   BASIC LOCAL ALIGNMENT SEARCH TOOL [J].
ALTSCHUL, SF ;
GISH, W ;
MILLER, W ;
MYERS, EW ;
LIPMAN, DJ .
JOURNAL OF MOLECULAR BIOLOGY, 1990, 215 (03) :403-410
[5]  
Barrett T, 2005, NUCLEIC ACIDS RES, V33, pD562
[6]  
Bell SE, 2001, J CELL SCI, V114, P2755
[7]   Vascular endothelial growth factor-induced signaling pathways in endothelial cells that mediate overexpression of the chemokine IFN-γ-Inducible protein of 10 kDa in vitro and in vivo [J].
Boulday, Gwenola ;
Haskova, Zdenka ;
Reinders, Marlies E. J. ;
Pal, Soumitro ;
Briscoe, David M. .
JOURNAL OF IMMUNOLOGY, 2006, 176 (05) :3098-3107
[8]   Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele [J].
Carmeliet, P ;
Ferreira, V ;
Breier, G ;
Pollefeyt, S ;
Kieckens, L ;
Gertsenstein, M ;
Fahrig, M ;
Vandenhoeck, A ;
Harpal, K ;
Eberhardt, C ;
Declercq, C ;
Pawling, J ;
Moons, L ;
Collen, D ;
Risau, W ;
Nagy, A .
NATURE, 1996, 380 (6573) :435-439
[9]   Angiogenesis in health and disease [J].
Carmeliet, P .
NATURE MEDICINE, 2003, 9 (06) :653-660
[10]   Dual functional roles of Tie-2/angiopoietin in TNF-α-mediated angiogenesis [J].
Chen, JX ;
Chen, Y ;
DeBusk, L ;
Lin, WY ;
Lin, PC .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2004, 287 (01) :H187-H195