Fibroblast growth factor 9 delivery during angiogenesis produces durable, vasoresponsive microvessels wrapped by smooth muscle cells

被引：92

作者：

Frontini, Matthew J. ^{[1
,2
,4
]}

Nong, Zengxuan ^{[1
,2
]}

Gros, Robert ^{[1
,2
,6
]}

Drangova, Maria ^{[1
,2
,5
]}

O'Neil, Caroline ^{[1
,2
]}

Rahman, Mona N. ^{[1
,2
]}

Akawi, Oula ^{[1
,2
]}

Yin, Hao ^{[1
,2
]}

Ellis, Christopher G. ^{[5
]}

Pickering, J. Geoffrey ^{[1
,2
,3
,4
,5
]}

机构：

[1] Univ Western Ontario, Schulich Sch Med & Dent, Robarts Res Inst, London, ON, Canada

[2] London Hlth Sci Ctr, London, ON, Canada

[3] Univ Western Ontario, Schulich Sch Med & Dent, Dept Med Cardiol, London, ON, Canada

[4] Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON, Canada

[5] Univ Western Ontario, Dept Med Biophys, Schulich Sch Med & Dent, London, ON, Canada

[6] Univ Western Ontario, Dept Physiol & Pharmacol, Schulich Sch Med & Dent, London, ON, Canada

来源：

NATURE BIOTECHNOLOGY | 2011年 / 29卷 / 05期

基金：

加拿大健康研究院;

关键词：

ENDOTHELIAL-CELLS; THERAPEUTIC ANGIOGENESIS; HINDLIMB ISCHEMIA; GENE-THERAPY; IN-VIVO; PDGF-BB; MOUSE; NEOVASCULARIZATION; DIFFERENTIATION; DISEASE;

D O I：

10.1038/nbt.1845

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The therapeutic potential of angiogenic growth factors has not been realized. This may be because formation of endothelial sprouts is not followed by their muscularization into vasoreactive arteries. Using microarray expression analysis, we discovered that fibroblast growth factor 9 (FGF9) was highly upregulated as human vascular smooth muscle cells (SMCs) assemble into layered cords. FGF9 was not angiogenic when mixed with tissue implants or delivered to the ischemic mouse hind limb, but instead orchestrated wrapping of SMCs around neovessels. SMC wrapping in implants was driven by sonic hedgehog-mediated upregulation of PDGFRb. Computed tomography microangiography and intravital microscopy revealed that microvessels formed in the presence of FGF9 had enhanced capacity to receive flow and were vasoreactive. Moreover, the vessels persisted beyond 1 year, remodeling into multilayered arteries paired with peripheral nerves. This mature physiological competency was attained by targeting mesenchymal cells rather than endothelial cells, a finding that could inform strategies for therapeutic angiogenesis and tissue engineering.

引用

页码：421 / U232

页数：9

共 47 条

[1] FatiGO:: a web tool for finding significant associations of Gene Ontology terms with groups of genes [J].

Al-Shahrour, F ;

Díaz-Uriarte, R ;

Dopazo, J .

BIOINFORMATICS, 2004, 20 (04) :578-580

[2]

Benjamin LE, 1998, DEVELOPMENT, V125, P1591

[3] Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2 [J].

Cao, RH ;

Bråkenhielm, E ;

Pawliuk, R ;

Wariaro, D ;

Post, MJ ;

Wahlberg, E ;

Leboulch, P ;

Cao, YH .

NATURE MEDICINE, 2003, 9 (05) :604-613

[4] Telomere measurement by quantitative PCR [J].

Cawthon, RM .

NUCLEIC ACIDS RESEARCH, 2002, 30 (10) :e47

[5] Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened [J].

Chen, JK ;

Taipale, J ;

Cooper, MK ;

Beachy, PA .

GENES & DEVELOPMENT, 2002, 16 (21) :2743-2748

[6]

Colvin JS, 2001, DEVELOPMENT, V128, P2095

[7] DAVID: Database for annotation, visualization, and integrated discovery [J].

Dennis, G ;

Sherman, BT ;

Hosack, DA ;

Yang, J ;

Gao, W ;

Lane, HC ;

Lempicki, RA .

GENOME BIOLOGY, 2003, 4 (09)

[8] Lipid Incorporation Inhibits Src-Dependent Assembly of Fibronectin and Type I Collagen by Vascular Smooth Muscle Cells [J].

Frontini, Matthew J. ;

O'Neil, Caroline ;

Sawyez, Cynthia ;

Chan, Bosco M. C. ;

Huff, Murray W. ;

Pickering, J. Geoffrey .

CIRCULATION RESEARCH, 2009, 104 (07) :832-U40

[9] Fgf9 signaling regulates small intestinal elongation and mesenchymal development [J].

Geske, Michael J. ;

Zhang, Xiuqin ;

Patel, Khushbu K. ;

Ornitz, David M. ;

Stappenbeck, Thaddeus S. .

DEVELOPMENT, 2008, 135 (17) :2959-2968

[10] Human Studies of Angiogenic Gene Therapy [J].

Gupta, Rajesh ;

Tongers, Joern ;

Losordo, Douglas W. .

CIRCULATION RESEARCH, 2009, 105 (08) :724-736

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