血管生成评价方法和模型研究进展
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摘要
血管生成(angiogenesis)系指从已有的毛细血管或毛细血管后静脉发展形成新血管的过程。血管生成主要发生在出生后,是许多血管结构形成的基础,参与体内多种生理、病理过程。由于研究对象的特殊性和种属的差异性,某一种模型得到的实验结果未必能在另一种模型上得到确证,目前全面评价受试因素对血管生成的影响一般需要不同模型结果的相互印证。笔者综述了国内外近十年血管生成相关文献,从细胞、组织、整体水平对目前公认度较高的主要评价方法与实验模型进行归纳,以期为血管生成相关药物研发及活性评价提供依据。
Angiogenesis,the process of shaping new vessels from existing or posteriorvessels. It occurs mainly after birth and is the basis for the formation of many vascular structures and participates ina variety of physiological and pathological processes. Due to the particularity of the research objects and the diversity of the species,the experimental results obtained from one model may not be confirmed on the other model. At present,the comprehensive evaluation of angiogenesis requires mutual verification of different model results. Herein,this review mainly summarizes the literatures on the evaluation of angiogenesis activity within recent ten years. From three parallel dimensions of cell,tissue,and animal,the up-to-date evaluation methods and angiogenesis models with wide recognitions are reviewed,in order to provide the reference for related drug research and development.
Angiogenesis,the process of shaping new vessels from existing or posteriorvessels. It occurs mainly after birth and is the basis for the formation of many vascular structures and participates ina variety of physiological and pathological processes. Due to the particularity of the research objects and the diversity of the species,the experimental results obtained from one model may not be confirmed on the other model. At present,the comprehensive evaluation of angiogenesis requires mutual verification of different model results. Herein,this review mainly summarizes the literatures on the evaluation of angiogenesis activity within recent ten years. From three parallel dimensions of cell,tissue,and animal,the up-to-date evaluation methods and angiogenesis models with wide recognitions are reviewed,in order to provide the reference for related drug research and development.
引文
[1]UDAN R S,CULVER J C,DICKINSON M E.Understanding vascular development[J].Develop Biol,2013,2(3):327-346.
[2]RIBATTI D,NICO B,CRIVELLATO E.The development of the vascular system:a historical overview[J].Methods Mol Biol,2015,1214:1-14.
[3]JAYSON G C,KERBEL R,ELLIS L M,et al.Antiangiogenic therapy in oncology:current status and future directions[J].Lancet,2016,388(10043):518-529.
[4]BONAPACE L,COISSIEUX M M,WYCKOFF J,et al.Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis[J].Nature,2014,515(7525):130-133.
[5]DE BOCK K,GEORGIADOU M,SCHOORS S,et al.Role of PFKFB3-driven glycolysis in vessel sprouting[J].Cell,2013,154(3):651-663.
[6]BAKER M,ROBINSON S D,LECHERTIER T,et al.Use of the mouse aortic ring assay to study angiogenesis[J].Nat Protoc,2011,7(1):89-104.
[7]HONG X,ZHONG C,NUDLEMAN E,et al.Evidence for proangiogenic functions of VEGF-Ax[J].Cell,2016,167(1):275-284.
[8]ADAMS R H,EICHMANN A.Axon guidance molecules in vascular patterning[J].Cold Spring Harb Perspect Biol,2010,2(5):a001875.
[9]RAMESHBABU A P,BANKOTI K,DATTA S,et al.Silk sponges ornamented with placenta-derived extracellular matrix augments full-thickness cutaneous wound healing by stimulating neovascularization and cellular migration[J].ACS Appl Mater Interfaces,2018,10(20):16977-16991.
[10]RED-HORSE K,UENO H,WEISSMAN I L,et al.Coronary arteries form by developmental reprogramming of venous cells[J].Nature,2010,464(7288):549-553.
[11]TAMMELA T,ZARKADA G,WALLGARD E,et al.Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation[J].Nature,2008,454(7204):656-660.
[12]ZAHALKA A H,ARNAL-ESTAPA,MARYANOVICH M,et al.Adrenergic nerves activate an angio-metabolic switch in prostate cancer[J].Science,2017,358(6361):321-326.
[13]RAHBARI N N,KEDRIN D,INCIO J,et al.Anti-VEGF therapy induces ECM remodeling and mechanical barriers to therapy in colorectal cancer liver metastases[J].Sci Transl Med,2016,8:360ra135.
[14]SEANO G,CHIAVERINA G,GAGLIARDI P A,et al.Endothelial podosome rosettes regulate vascular branching in tumour angiogenesis[J].Nat Cell Biol,2014,16(10):931-941.
[15]POTENTE M,MKINEN T.Vascular heterogeneity and specialization in development and disease[J].Nat Rev Mol Cell Biol,2017,18(8):477-494.
[16]KIM M H,JEONG Y J,CHO H J,et al.Delphinidin inhibits angiogenesis through the suppression of HIF-1αand VEGF expression in A549 lung cancer cells[J].Oncol Reports,2016,37(2):777-784.
[17]LONGCHAMP A,MIRABELLA T,HINE C,et al.Angiogenesis is triggered by nutrient deprivation via Gcn2/atf4-dependent regulation of Vegf and H2Sproduction[J].Cell,2018,173(1):117-129.
[18]DAS A,HUANG G S,BONKOWSKI M S,et al.Impairment of an endothelial NAD+-H2S signaling network is a reversible cause of vascular aging[J].Cell,2018,173(4):74-89.
[19]YU L,WU X,CHENG Z,et al.Interaction between bevacizumab and murine VEGF-A:a reassessment[J].Invest Ophthalmol Vis Sci,2008,49(2):522-527.
[20]XING Y H,LIU G,CHEN H P.Models of tumor angiogenesis assay[J].Lett Biotechnol,2012,3:444-447.
[21]YU P,WILHELM K,DUBRAC A,et al.FGF-dependent metabolic control of vascular development[J].Nature,2017,545(7653):224-228.
[22]WANG X,ABRAHAM S,MCKENZIE J A,et al.LRG1 promotes angiogenesis by modulating endothelial TGF-βsignaling[J].Nature,2013,499(7458):306-311.
[23]SCHOORS S,BRUNING U,MISSIAEN R,et al.Fatty acid carbon is essential for dNTP synthesis in endothelial cells[J].Nature,2015,520(7546):192-197.
[24]FINISGUERRA V,DI G C,DI M M,et al.MET is required for the recruitment of anti-tumoural neutrophils[J].Nature,2015,522(7556):349-353.
[25]OOMMEN S,GUPTA S K,VLAHAKIS N E.Vascular endothelial growth factor A(VEGF-A)induces endothelial and cancer cell migration through direct binding to integrin alpha9 beta1:identification of a specific alpha9beta1 binding site[J].J Biol Chem,2011,286(2):1083-1092.
[26]BORRADAILE N M,PICKERING J G.Nicotinamide phosphoribosyltransferase imparts human endothelial cells with extended replicative lifespan and enhanced angiogenic capacity in a high glucose environment[J].Aging Cell,2009,8(2):100-112.
[27]ARNAOUTOVA I,KLEINMAN H K.In vitro angiogenesis:endothelial cell tube formation on gelled basement membrane extract[J].Nat Protoc,2010,5(4):628-635.
[28]KORFF T,AUGUSTIN H G.Integration of endothelial cells in multicellular spheroids prevents apoptosis and induces differentiation[J].J Cell Biol,1998,143(5):1341-1352.
[29]DE B K,GEORGIADOU M,SCHOORS S,et al.Role of PFKFB3-driven glycolysis in vessel sprouting[J].Cell,2013,154(3):651-663.
[30]NICOSIA R F,OTTINETTI A.Growth of microvessels in serumfree matrix culture of rat aorta.A quantitative assay of angiogenesis in vitro[J].Lab Invest,1990,63(1):115-122.
[31]DECKERS M,VAN D P G,DOOIJEWAARD S,et al.Effect of angiogenic and antiangiogenic compounds on the outgrowth of capillary structures from fetal mouse bone explants[J].Lab Invest,2001,81(1):5-15.
[32]SAWAMIPHAK S,RITTER M,ACKER-PALMER A.Preparation of retinal explant cultures to study ex vivo tip endothelial cell responses[J].Nat Protoc,2010,5(10):1659-1665.
[33]YUEN T J,SILBEREIS J C,GRIVEAU M,et al.Oligodendrocyte-encoded HIF function couples postnatal myelination and white matter angiogenesis[J].Cell,2014,158(2):383-396.
[34]MOSCONA A,CARNECKAS Z I.Etiology of keratogenic metaplasia in the chorioallantoic membrane[J].Science,1959,129(3365):1743-1744.
[35]BANERJEE R,RUSSO N,LIU M,et al.TRIP13 promotes error-prone nonhomologous end joining and induces chemoresistance in head and neck cancer[J].Nat Commun,2014,5:4527-4563.
[36]OEHLERS S H,CRONAN M R,SCOTT N R,et al.Interception of host angiogenic signalling limits mycobacterial growth[J].Nature,2015,517(7536):612-615.
[37]OKABE K,KOBAYASHI S,YAMADA T,et al.Neurons limit angiogenesis by titrating VEGF in retina[J].Cell,2014,159(3):584-596.
[38]WILHELM K,HAPPEL K,EELEN G,et al.FOXO1 couples metabolic activity and growth state in the vascular endothelium[J].Nature,2016,529(7585):216-220.
[39]ZHOU H J,XU Z,WANG Z,et al.Sumoylation of VEGFR2regulates its intracellular trafficking and pathological angiogenesis[J].Nat Commun,2018,9(1):3303.
[40]WHITEUS C,FREITAS C,GRUTZENDLER J.Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period[J].Nature,2014,505(7483):407-411.
[41]CROCI D O,CERLIANI J P,DALOTTOMORENO T,et al.Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors[J].Cell,2014,156(4):744-758.
[42]ZHAO L G,LIU Z G,YANG A H.Stachydrine inhibits the growth of colon cancer by regulating the expression of ACTG2[J].Chin Pharm J(中国药学杂志),2018,53(13):1077-1082.
[43]LIU T,MA W,XU H,et al.PDGF-mediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma[J].Nat Commun,2018,9(1):3439-3441.
[44]WANG Y,WU B,LU P,et al.Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut 1[J].Nat Commun,2017,8(1):578-590.
[45]WU S Y,RUPAIMOOLE R,SHEN F,et al.A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer[J].Nat Commun,2016,7:11169.
[46]ZHANG Y,ZHENG D Y,ZHOU T,et al.Androgen deprivation promotes neuroendocrine differentiation and angiogenesis through CREB-EZH2-TSP1 pathway in prostate cancers[J].Nat Commun,2018,9(1):4080.
[47]DONNEM T,REYNOLDS A R,KUCZYNSKI E A,et al.Nonangiogenic tumours and their influence on cancer biology[J].Nat Rev Cancer,2018,18(5):323-336.
[48]SEANO G,CHIAVERINA G,GAGLIAROI P A,et al.Endothelial podosome rosettes regulate vascular branching in tumour angiogenesis[J].Nat Cell Biol,2014,16(10):931-941.
[49]NIH L R,GOJGINI S,CARMICHAEL S T,et al.Dual-function injectable angiogenic biomaterial for the repair of brain tissue following stroke[J].Nat Mater,2018,17(7):642-651.
[50]LI X,CARMELIET P.Targeting angiogenic metabolism in disease[J].Science,2018,359(6382):1335-1336.
[2]RIBATTI D,NICO B,CRIVELLATO E.The development of the vascular system:a historical overview[J].Methods Mol Biol,2015,1214:1-14.
[3]JAYSON G C,KERBEL R,ELLIS L M,et al.Antiangiogenic therapy in oncology:current status and future directions[J].Lancet,2016,388(10043):518-529.
[4]BONAPACE L,COISSIEUX M M,WYCKOFF J,et al.Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis[J].Nature,2014,515(7525):130-133.
[5]DE BOCK K,GEORGIADOU M,SCHOORS S,et al.Role of PFKFB3-driven glycolysis in vessel sprouting[J].Cell,2013,154(3):651-663.
[6]BAKER M,ROBINSON S D,LECHERTIER T,et al.Use of the mouse aortic ring assay to study angiogenesis[J].Nat Protoc,2011,7(1):89-104.
[7]HONG X,ZHONG C,NUDLEMAN E,et al.Evidence for proangiogenic functions of VEGF-Ax[J].Cell,2016,167(1):275-284.
[8]ADAMS R H,EICHMANN A.Axon guidance molecules in vascular patterning[J].Cold Spring Harb Perspect Biol,2010,2(5):a001875.
[9]RAMESHBABU A P,BANKOTI K,DATTA S,et al.Silk sponges ornamented with placenta-derived extracellular matrix augments full-thickness cutaneous wound healing by stimulating neovascularization and cellular migration[J].ACS Appl Mater Interfaces,2018,10(20):16977-16991.
[10]RED-HORSE K,UENO H,WEISSMAN I L,et al.Coronary arteries form by developmental reprogramming of venous cells[J].Nature,2010,464(7288):549-553.
[11]TAMMELA T,ZARKADA G,WALLGARD E,et al.Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation[J].Nature,2008,454(7204):656-660.
[12]ZAHALKA A H,ARNAL-ESTAPA,MARYANOVICH M,et al.Adrenergic nerves activate an angio-metabolic switch in prostate cancer[J].Science,2017,358(6361):321-326.
[13]RAHBARI N N,KEDRIN D,INCIO J,et al.Anti-VEGF therapy induces ECM remodeling and mechanical barriers to therapy in colorectal cancer liver metastases[J].Sci Transl Med,2016,8:360ra135.
[14]SEANO G,CHIAVERINA G,GAGLIARDI P A,et al.Endothelial podosome rosettes regulate vascular branching in tumour angiogenesis[J].Nat Cell Biol,2014,16(10):931-941.
[15]POTENTE M,MKINEN T.Vascular heterogeneity and specialization in development and disease[J].Nat Rev Mol Cell Biol,2017,18(8):477-494.
[16]KIM M H,JEONG Y J,CHO H J,et al.Delphinidin inhibits angiogenesis through the suppression of HIF-1αand VEGF expression in A549 lung cancer cells[J].Oncol Reports,2016,37(2):777-784.
[17]LONGCHAMP A,MIRABELLA T,HINE C,et al.Angiogenesis is triggered by nutrient deprivation via Gcn2/atf4-dependent regulation of Vegf and H2Sproduction[J].Cell,2018,173(1):117-129.
[18]DAS A,HUANG G S,BONKOWSKI M S,et al.Impairment of an endothelial NAD+-H2S signaling network is a reversible cause of vascular aging[J].Cell,2018,173(4):74-89.
[19]YU L,WU X,CHENG Z,et al.Interaction between bevacizumab and murine VEGF-A:a reassessment[J].Invest Ophthalmol Vis Sci,2008,49(2):522-527.
[20]XING Y H,LIU G,CHEN H P.Models of tumor angiogenesis assay[J].Lett Biotechnol,2012,3:444-447.
[21]YU P,WILHELM K,DUBRAC A,et al.FGF-dependent metabolic control of vascular development[J].Nature,2017,545(7653):224-228.
[22]WANG X,ABRAHAM S,MCKENZIE J A,et al.LRG1 promotes angiogenesis by modulating endothelial TGF-βsignaling[J].Nature,2013,499(7458):306-311.
[23]SCHOORS S,BRUNING U,MISSIAEN R,et al.Fatty acid carbon is essential for dNTP synthesis in endothelial cells[J].Nature,2015,520(7546):192-197.
[24]FINISGUERRA V,DI G C,DI M M,et al.MET is required for the recruitment of anti-tumoural neutrophils[J].Nature,2015,522(7556):349-353.
[25]OOMMEN S,GUPTA S K,VLAHAKIS N E.Vascular endothelial growth factor A(VEGF-A)induces endothelial and cancer cell migration through direct binding to integrin alpha9 beta1:identification of a specific alpha9beta1 binding site[J].J Biol Chem,2011,286(2):1083-1092.
[26]BORRADAILE N M,PICKERING J G.Nicotinamide phosphoribosyltransferase imparts human endothelial cells with extended replicative lifespan and enhanced angiogenic capacity in a high glucose environment[J].Aging Cell,2009,8(2):100-112.
[27]ARNAOUTOVA I,KLEINMAN H K.In vitro angiogenesis:endothelial cell tube formation on gelled basement membrane extract[J].Nat Protoc,2010,5(4):628-635.
[28]KORFF T,AUGUSTIN H G.Integration of endothelial cells in multicellular spheroids prevents apoptosis and induces differentiation[J].J Cell Biol,1998,143(5):1341-1352.
[29]DE B K,GEORGIADOU M,SCHOORS S,et al.Role of PFKFB3-driven glycolysis in vessel sprouting[J].Cell,2013,154(3):651-663.
[30]NICOSIA R F,OTTINETTI A.Growth of microvessels in serumfree matrix culture of rat aorta.A quantitative assay of angiogenesis in vitro[J].Lab Invest,1990,63(1):115-122.
[31]DECKERS M,VAN D P G,DOOIJEWAARD S,et al.Effect of angiogenic and antiangiogenic compounds on the outgrowth of capillary structures from fetal mouse bone explants[J].Lab Invest,2001,81(1):5-15.
[32]SAWAMIPHAK S,RITTER M,ACKER-PALMER A.Preparation of retinal explant cultures to study ex vivo tip endothelial cell responses[J].Nat Protoc,2010,5(10):1659-1665.
[33]YUEN T J,SILBEREIS J C,GRIVEAU M,et al.Oligodendrocyte-encoded HIF function couples postnatal myelination and white matter angiogenesis[J].Cell,2014,158(2):383-396.
[34]MOSCONA A,CARNECKAS Z I.Etiology of keratogenic metaplasia in the chorioallantoic membrane[J].Science,1959,129(3365):1743-1744.
[35]BANERJEE R,RUSSO N,LIU M,et al.TRIP13 promotes error-prone nonhomologous end joining and induces chemoresistance in head and neck cancer[J].Nat Commun,2014,5:4527-4563.
[36]OEHLERS S H,CRONAN M R,SCOTT N R,et al.Interception of host angiogenic signalling limits mycobacterial growth[J].Nature,2015,517(7536):612-615.
[37]OKABE K,KOBAYASHI S,YAMADA T,et al.Neurons limit angiogenesis by titrating VEGF in retina[J].Cell,2014,159(3):584-596.
[38]WILHELM K,HAPPEL K,EELEN G,et al.FOXO1 couples metabolic activity and growth state in the vascular endothelium[J].Nature,2016,529(7585):216-220.
[39]ZHOU H J,XU Z,WANG Z,et al.Sumoylation of VEGFR2regulates its intracellular trafficking and pathological angiogenesis[J].Nat Commun,2018,9(1):3303.
[40]WHITEUS C,FREITAS C,GRUTZENDLER J.Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period[J].Nature,2014,505(7483):407-411.
[41]CROCI D O,CERLIANI J P,DALOTTOMORENO T,et al.Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors[J].Cell,2014,156(4):744-758.
[42]ZHAO L G,LIU Z G,YANG A H.Stachydrine inhibits the growth of colon cancer by regulating the expression of ACTG2[J].Chin Pharm J(中国药学杂志),2018,53(13):1077-1082.
[43]LIU T,MA W,XU H,et al.PDGF-mediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma[J].Nat Commun,2018,9(1):3439-3441.
[44]WANG Y,WU B,LU P,et al.Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut 1[J].Nat Commun,2017,8(1):578-590.
[45]WU S Y,RUPAIMOOLE R,SHEN F,et al.A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer[J].Nat Commun,2016,7:11169.
[46]ZHANG Y,ZHENG D Y,ZHOU T,et al.Androgen deprivation promotes neuroendocrine differentiation and angiogenesis through CREB-EZH2-TSP1 pathway in prostate cancers[J].Nat Commun,2018,9(1):4080.
[47]DONNEM T,REYNOLDS A R,KUCZYNSKI E A,et al.Nonangiogenic tumours and their influence on cancer biology[J].Nat Rev Cancer,2018,18(5):323-336.
[48]SEANO G,CHIAVERINA G,GAGLIAROI P A,et al.Endothelial podosome rosettes regulate vascular branching in tumour angiogenesis[J].Nat Cell Biol,2014,16(10):931-941.
[49]NIH L R,GOJGINI S,CARMICHAEL S T,et al.Dual-function injectable angiogenic biomaterial for the repair of brain tissue following stroke[J].Nat Mater,2018,17(7):642-651.
[50]LI X,CARMELIET P.Targeting angiogenic metabolism in disease[J].Science,2018,359(6382):1335-1336.