Abstract
This review of angiogenesis aims to describe (a) stimuli that either elicit or antagonize angiogenesis, (b) the response of the vasculature to angiogenic or antiangiogenic stimuli, i.e., processes required for the formation of new vessels, (c) aspects of angiogenesis relating to tissue remodeling and disease, and (d) the potential of angiogenic or antiangiogenic therapeutic measures. Angiogenesis, the formation of new vessels from existing microvessels, is important in embryogenesis, wound healing, diabetic retinopathy, tumor growth, and other diseases. Hypoxia and other as yet ill-defined stimuli drive tumor, inflammatory, and connective tissue cells to generate angiogenic molecules such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), and others. Natural and synthetic angiogenesis inhibitors such as angiostatin and thalidomide can repress angiogenesis. Angiogenic and antiangiogenic molecules control the formation of new vessels via different mechanisms. VEGF and FGF elicit their effects mainly via direct action on relevant endothelial cells. TGF-β and PDGF can attract inflammatory or connective tissue cells which in turn control angiogenesis. Additionally, PDGF may act differently on specific phenotypes of endothelial cells that are engaged in angiogenesis or that are of microvascular origin. Thus phenotypic traits of endothelial cells committed to angiogenesis may determine their cellular responses to given stimuli. Processes necessary for new vessel formation and regulated by angiogenic/antiangiogenic molecules include the migration and proliferation of endothelial cells from the microvasculature, the controlled expression of proteolytic enzymes, the breakdown and reassembly of extracellular matrix, and the morphogenic process of endothelial tube formation. In animal models some angiogenesis-dependent diseases can be controlled via induction or inhibition of new vessel formation. Lifethreatening infantile hemangiomas are a first established indication for antiangiogenic therapy in humans. Treatment of other diseases by modulation of angiogenesis are currently tested in clinical trials. Thus the manipulation of new vessel formation in angiogenesis-dependent conditions such as wound healing, inflammatory diseases, ischemic heart and peripheral vascular disease, myocardial infarction, diabetic retinopathy, and cancer is likely to create new therapeutic options.
Similar content being viewed by others
Abbreviations
- VEGF :
-
Vascular endothelial growth factor
- FGF :
-
Fibroblast growth factor
- TGF :
-
Transforming growth factor
- PDGF :
-
Platelet-derived growth factor
- CAM :
-
Chorionic allantoic membrane assay
References
Adamis AP, Miller JW, Bernal MT, D'Amico DJ, Folkman J, Yeo TK, Yeo KT (1994) Elevated vascular permeability factor/vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 118:445–450
Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, Nguyen HV, Aiello LM, Ferrara N, King GL (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal diseases. N Engl J Med 331:1480–1487
Anagnostou Z, Liu Z, Steiner M, Chin K, Lee ES, Kessimian N, Noguchi CT (1994) Erythropoietin receptor mRNA expression in human endothelial cells. Proc Natl Acad Sci USA 91:3974–3978
Antonelli-Orlidge A, Saunders KB, Smith SR, D'Amore PA (1989) An activated form of transforming growth factor β is produced by cocultures of endothelial cells and pericytes. Proc Natl Acad Sci USA 86:4544–4548
Ausprunk DH, Folkman J (1977) Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during angiogenesis. Microvasc Res 14:53–65
Baird A, Böhlen P (1990) Fibroblast growth factors. In; Sporn MB Roberts AB (eds) Peptide growth factors and their receptors I. Springer, Berlin Heidelberg New York, pp 369–418
Bar RS, Boes M, Booth BA, Dake BL, Henley S, Hart MN (1989) The effects of platelet-derived growth factor in cultured microvessel endothelial cells. Endocrinology 124:1841–1848
Barger CA, Beeuwkes R, Lainley L, Silverman KJ (1984) Hypothesis: vasa vasorum and neovascularization of human coronary arteries. N Engl J Med 310:175–177
Barnhill RL, Levy MA (1993) Regressing thin cutaneous malignant melanomas (< or =1.0 mm) are associated with angiogenesis. Am J Pathol 143:99–104
Battegay EJ, Raines EW, Seifert RA, Bowen-Pope DF, Ross R (1990) TGF-β induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop. Cell 63:515–524
Battegay EJ, Rupp J, Iruela-Arispe L, Sage EH, Pech M (1994) PDGF-BB modulates endothelial proliferation and angiogenesis in vitro via PDGF β-receptors. J Cell Biol 125:917–928
Battler A, Scheinowitz AM, Bor A, Hasdai D, Vered Z, DiSegni E, Varda-Bloom N, Nass D, Engelberg S, Eldar M, et al (1993) Intracoronary injection of basic fibroblast growth factor enhances angiogenesis in infarcted swine myocardium. J Am Coll Cardiol 22:2001–2006
Beekhuizen H, Corsel-van Tilburg AJ, van Furth R (1990) Characterization of monocyte adherence to human macrovascular and microvascular endothelial cells. J of Immunol 145:510–518
Beitz JG, Kim IS, Calabresi P, Frackelton ARJ (1991) Human microvascular endothelial cells express receptors for platelet-derived growth factor. Proc Natl Acad Sci USA 88:2021–2025
Berkman RA, Merrill MJ, Reinhold WC, Monacci WT, Saxena A, Clark WC, Robertson JT, Ali IU, Oldfield E (1993) Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms. J Clin Invest 91:153–159
Bicknell R (1994) Vascular targeting and the inhibition of angiogenesis. Ann Oncol 5 [Suppl] 4:45–50
Blei F, Wilson EL, Mignatti P, Rifkin DB (1993) Mechanism of action of angiostatic steroids: suppression of plasminogen activator activity via stimulation of plasminogen activator inhibitor synthesis. J Cell Physiol 155:568–578
Breier G, Albrecht U, Sterrer S, Risau W (1992) Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development 114:521–532
Brindle NPJ (1993) Growth factors in endothelial regeneration. Cardiovasc Res 27:1162–1172
Broadley KN, Aquino AM, Hicks B, Ditesheim JA, McGee GS, Demetriou AA, Woodward SC, Davidson JM (1989) The diabetic rat as an impaired wound healing model: stimulatory effects of transforming growth factor-beta and basic fibroblast growth factor. Biotechnol Ther 1:55–68
Brogi E, Wu T, Namiki A, Isner JM (1994) Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth muscle cells, whereas hypoxia upregulates VEGF expression only. Circulation 90:649–652
Brooks PC, Clark RA, Cheresh DA (1994) Requirement of vascular integrin αvβ3 for angiogenesis. Science 264:569–571
Brooks PC, Montgomery AMP, Rosenfeld M, Reisfeld RA, Hu T, Klier G, Cheresh DA (1994) Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 79:1157–1164
Brown RL, Breeden MP, Greenhalgh DG (1994) PDGF and TGF-β act synergistically to improve wound healing in the genetically diabetic mouse. J Surg Res 56:562–570
Bussolino F, Di Renzo MF, Ziche M, Bocchietto E, Olivero M, Naldini L, Gaudino G, Tamagnone L, Coffer A, Comoglio P (1992) Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. J Cell Biol 119:629–641
Carmeliet P, Schoonjans L, Kieckens L, Ream B, Degen J, Bronson R, De Vos R, van den Oord JJ, Collen D, Mulligan RC (1994) Physiological consequences of loss of plasminogen activator gene function in mice. Nature 368:419–424
Chen HH, Chien CH, Liu HM (1994) Correlation between angiogenesis and basic fibroblast growth factor expression in experimental brain infarct. Stroke 25:1651–1657
Cid MC, Grant DS, Hoffman GS, Auerbach R, Fauci AS, Kleinman HK (1993) Identification of haptoglobin as an angiogenic factor in sera from patients with systemic vasculitis. J Clin Invest 91:977–985
Clapp C, Martial JA, Guzman RC, Rentier-Delure F, Weiner RI (1993) The 16-kilodalton N-terminal fragment of human prolactin is a potent inhibitor of angiogenesis. Endocrinology 133:1292–1296
Craft PS, Harris AL (1994) Clinical prognostic significance of tumour angiogenesis. Ann Oncol 5:305–311
D'Amato RJ, Loughnan MS, Flynn E, Folkman J (1994) Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 91:4082–4085
Dameron KM, Volpert OV, Tainsky MA, Bouck N (1994) Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science 265:1582–1584
Denijn M, Ruiter DJ (1993) The possible role of angiogenesis in the metastatic potential of human melanoma. Clinicopathological aspects. Melanoma Res 3:5–14
DiPietro LA, Polverini PJ (1993) Angiogenic macrophages produce the angiogenic inhibitor thrombospondin 1. Am J Pathol 143:678–684
DiPietro LA, Nebgen DR, Polverini PJ (1994) Downregulation of endothelial cell thrombospondin 1 enhances in vitro angiogenesis. J Vasc Res 31:178–185
Dissen GA, Lara HE, Fahrenbach WH, Costa ME, Ojeda SR (1994) Immature rat ovaries become revascularized rapidly after autotransplantation and show a gonadotropin-dependent increase in angiogenic factor gene expression. Endocrinology 134:1146–1154
Dupuy E, Bikfalvi A, Rendu F, Levy-Toledano S, Tobelem G (1989) Thrombin mitogenic responses and protein phosphorylation are different in cultured human endothelial cells derived from large and microvessels. Exp Cell Res 185:363–372
Ensoli B, Gendelman R, Markham P, Fiorelli V, Colombini S, Raffeld M, Cafaro A, Chang HK, Brady JN, Gallo RC (1994) Synergy between basic fibroblast growth factor and HIV-1 tat protein in induction of Kaposi's sarcoma. Nature 371:674–680
Ensoli B, Markham P, Kao V, Barillari G, Fiorelli V, Gendelman R, Raffeld M, Zon G, Gallo R (1994) Block of AIDS-Kaposi's sarcoma (KS) cell growth, angiogenesis, and lesion formation in nude mice by antisense oligonucleotide targeting basic fibroblast growth factor. A novel strategy for the therapy of KS. J Clin Invest 94:1736–1746
Ezekowitz RA, Mulliken JB, Folkman J (1992) Interferon-2a therapy for life-threatening hemangiomas of infancy. N Engl J Med 326:1456–1463
Fava RA, Olsen NJ, Spencer Green G, Yeo KT, Yeo TK, Berse B, Jackman RW, Senger DR, Dvorak HF, Brown LF (1994) Vascular permeability factor/endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids and rheumatoid synovial tissue. J Exp Med 180:341–346
Ferrara N, Winer J, Henzel WJ (1992) Pituitary follicular cells secrete an inhibitor of aortic endothelial cell growth: identification as leukemia inhibitory factor. Proc Natl Acad Sci USA 89:698–702
Fisher JW, Nakashima J (1992) Kidney regulation of erythropoietin production. In Biochemical pharmacology of blood and bloodforming organs. Fisher JW (ed) Springer, Berlin Heidelberg New York, pp 33–48
Folkman J (1985) Toward an understanding of angiogenesis: search and discovery. Persp Biol Med 29:10–36
Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nature Med 1:27–31
Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931–10934
Forsberg K, Valyi-Nagy I, Heldin CH, Herlyn M, Westermark B (1993) Platelet-derived growth factor (PDGF) in oncogenesis: development of a vascular connective tissue stroma in xenotransplanted human melanoma producing PDGF-BB. Proc Natl Acad Sci USA 90:393–397
Fotsis T, Zhang Y, Pepper MS, Adlercreutz H, Montesano R, Nawroth PP, Schweigerer L (1994) The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature 368:237–239
Frank RM (1994) Vascular endothelial growth factor-its role in retinal vascular proliferation. N Engl J Med 331:1519–1520
Galis ZS, Sukhova GK, Lark MW, Libby P (1994) Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 94:2493–2503
Gasparini G, Weidner N, Bevilacqua P, Maluta S, Dalla Palma P, Caffo O, Barbareschi M, Boracchi P, Marubini E, Pozza F (1994) Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma. J Clin Oncol 12:454–466
Goldberg MA, Schneider TJ (1994) Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin. J Biol Chem 269:4355–4359
Graham CA, Rivers J, Kerbel RS, Stankiewicz KS, White WL (1994) Extent of vascularization as a prognostic indicator in thin (<0.76 mm) malignant melanomas. Am J Pathol 145:510–514
Grant DS, Kleinman HK, Goldberg ID, Bhargava MM, Nickoloff BJ, Kinsella JL, Polverini P, Rosen EM (1993) Scatter factor induces blood vessel formation in vivo. Proc Natl Acad Sci USA 90:1937–1941
Grant MB, Caballero S, Millard WJ (1993) Inhibition of IGF-I and b-FGF stimulated growth of human retinal endothelial cells by the somatostatin analogue, octreotide: a potential treatment for ocular neovascularization. Regul Pept 48:267–278
Grant MB, Mames RN, Fitzgerald C, Ellis EA, Aboufriekha M, Guy J (1993) Insulin-like growth factor I acts as an angiogenic agent in rabbit cornea and retina: comparative studies with basic fibroblast growth factor. Diabetologia 36:282–291
Gupta SK, Singh JP (1994) Inhibition of endothelial cell proiferation by platelet factor-4 involves a unique action on S phase progression. J Cell Biol 127:1121–1127
Harada K, Grossman W, Friedman M, Edelman ER, Prasad PV, Keighley CS, Manning WJ, Sellke FW, Simons M (1994) Basic fibroblast growth factor improves myocardial function in chronically ischemic porcine hearts. J Clin Invest 94:623–630
Haraguchi M, Miyadera K, Uemura K, Sumizawa T, Furukawa T, Yamada K, Akiyama S, Yamada Y (1994) Angiogenic activity of enzymes (letter). Nature 368:198
Heimark RL, Twardzik DR, Schwartz SM (1986) Inhibition of endothelial regeneration by type-beta transforming growth factor from platelets. Science 233:1078–1080
Hermanson M, Funa K, Hartman M, Claesson-Welsh L, Heldin CH, Westermark B, Nister M (1992) Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops. Cancer Res 52:3213–3219
Holmgren L, Glaser A, Pfeifer-Ohlsson S, Ohlsson R (1991) Angiogenesis during human extraembryonic development in 2 volves the spatiotemporal control of PDGF ligand and receptor gene expression. Development 113:749–754
Horak ER, Leek R, Klenk N, LeJeune S, Smith K, Stuart N, Greenall M, Stepniewska K, Harris AL (1992) Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet 340:1120–1124
Hori A, Sasada R, Matsutani E, Naito K, Sakura Y, Fujita T, Kozai Y (1991) Suppression of solid tumor growth by immunoneutralizing monoclonal antibody against human basic fibroblast growth factor. Cancer Res 51:6180–6184
Hull MA, Cullen DJE, Hawkey CJ (1994) Basic fibroblast growth factor in gastric ulceration: mucosal levels and therapeutic potential. Gastroenterology 106:A97
Ingber D (1991) Extracellular matrix and cell shape: potential control points for inhibition of angiogenesis. J Cell Biochem 47:236–241
Iruela-Arispe ML, Diglio CA, Sage EH (1991) Modulation of extracellular matrix by endothelial cells undergoing angiogenesis in vitro. Arterioscler Thromb 11:805–815
Iruela-Arispe ML, Hasselaar P, Sage H (1991) Differential expression of extracellular proteins is correlated with angiogenesis in vitro. Lab Invest 64:174–186
Iruela-Arispe ML, Sage EH (1993) Endothelial cells exhibiting angiogenesis in vitro proliferate in response to TGF-β1. J Cell Biochem 52:414–430
Jackson D, Volpert OV, Bouck N, Linzer DIH (1994) Stimulation and inhibition of angiogenesis by placental proliferin and proliferin-related protein. Science 266:1581–1584
Järveläinen HT, Iruela-Arispe ML, Kinsella MG, Sandell LJ, Sage EH (1992) Expression of decorin by sprouting bovine endothelial cells exhibiting angiogenesis in vitro. Exp Cell Res 203:395–401
Johnson MD, Kim HR, Chesler L, Tsao Wu G, Bouck N, Polverini PJ (1994) Inhibition of angiogenesis by tissue inhibitor of metalloproteinase. J Cell Physiol 160:194–202
Khouri RK, Hong SP, Deune EG, Tarpley JE, Song SZ, Serdar CM, Pierce GF (1994) De novo generation of permanent neovascularized soft tissue appendages by platelet-derived growth factor. J Clin Invest 94:1757–1763
Kim KJ, Li B, Winer J, Armanini M, Gillett NS, Phillips H, Ferrara N (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362:841–844
Klagsbrun M, Folkman J (1990) Angiogenesis. In: Sporn MB, Roberts AB (eds) Peptide growth factors and their receptors II. Springer, Berlin Heidelberg New York, pp 549–574
Koch AE, Polverini PJ, Kunkel SL, Harlow LA, DiPietro LA, Elner VM, Elner SG, Strieter R (1992) Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258:1798–1801
Koch AE, Harlow LA, Haines GK, Amento EP, Unemori EN, Wong W, Pope RM, Ferrara N (1994) Vascular endothelial growth factor. a cytokine modulating endothelial function in rheumatoid arthritis. J Immunol 152:4149–4156
Koester K (1876) Endarteriitis und Arteriitis. Klin Wochenschr 13:454–455
Koos RD (1989) Potential relevance of angiogenic factors to ovarian physiology Semin Reprod Endocrinol 7:29–40
Kourembanas S, Hannan RL, Faller DV (1990) Oxygen tension regulates the expression of platelet-derived growth factor-B chain gene in human endothelial cells. J Clin Invest 86:670–674
Kovacs EJ, DiPietro LA (1994) Fibrogenic cytokines and connective tissue production. FASEB. J 8:854–861
Lal B, Indurti RR, Couraud PO, Goldstein GW, Laterra J (1994) Endothelial cell implantation and survival within experimental gliomas. Proc Natl Acad Sci USA 91:9695–9699
Lane TF, Iruela-Arispe ML, Johnson RS, Sage EH (1994) SPARC is a source of copper-binding peptides that stimulate angiogenesis. J Cell Biol 125:929–943
Larsen WJ (1993) Human embryology Churchill Livingstone, New York. 435–452
LeGrand EK, Burke JF, Costa DE, Kiorpes TC (1993) Dose responsive effects of PDGF-BB, PDGF-AA, EGF, and bFGF on granulation tissue in a guinea pig partial thickness skin excision model. Growth. Factors. 8:307–314
Leibovich JS, Polverini PJ, Fong TW, Harlow LA, Koch AE (1994) Production of angiogenic activity by human monocytes requires an L-arginine/nitric oxide-synthase-dependent effector mechanism. Proc Natl Acad Sci USA 91:4190–4194
Liotta LA, Steeg PS, Stetler-Stevenson WG (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64:327–336
Loike JD, Brett L, Cao J, Ogawa S, Silverstein SC, Stern D (1994) Hypoxia induces glucose transporter expression in endothelial cells. Am J Physiol 263:C326-C233
Lüscher TF, Richard V, Tschudi M, Yang Z, Boulanger C (1990) Endothelial control of vascular tome in large and small coronary arteries. J Am Coll Cardiol 15:519–527
Lyons RM, Gentry LE, Purchio AE, Moses HL (1990) Mechanism of activation of latent recombinant transforming growth factor β1 by plasmin. J Cell Biol 110:1361–1367
Maglione D, Guerriero V, Viglietto G, Delli-Bovi P, Persico MG (1991) Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci USA 88:9267–9271
Maione TE, Gray GS, Petro J, Hunt AJ, Donner AL, Bauer SI, Carson HF, Sharpe RJ (1990) Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides. Science 247:77–79
Maragoudakis ME, Sarmonika M, Panoutsacopoulou M (1988) Inhibition of membrane biosynthesis prevents angiogenesis. J Pharmacol Exp Ther 244:729–733
Martins RN, Chleboun JO, Sellers P, Sleigh M, Muir J (1994) The role of PDGF-BB on the development of the collateral circulation after acute arterial occlusion. Growth Factors 10:299–306
Marx M, Perlmutter RA, Madri JA (1994) Modulation of platelet-derived growth factor receptor expression in microvascular endothelial cells during in vitro angiogenesis. J Clin Invest 93:131–139
McCaffrey TA, Falcone DJ, Brayton CF, Agarwal LA, Welt FGP, Weksler BB (1989) Transforming growth factor-β activity is potentiated by heparin via dissection of the transforming growth factor-β/α2-macroglobulin inactive complex. J Cell Biol 109:441–448
McNeil PL, Muthukrishnan L, Warder E, D'Amore PA (1989) Growth factors are released by mechanically wounded endothelial cells. J Cell Biol 109:811–822
Meyer-Schwickerath R, Pfeiffer A, Blum WF, Freyberger H, Klein M, Lösche C, Röllmann R, Schatz H (1994) Vitreous levels of the insulin-like growth factors I and II, and the insulin-like growth factor binding proteins 2 and 3, increase in neovascular eye disease. Studies in nondiabetic and diabetic subjects. J Clin Invest 92:2620–2625
Millauer B, Wizigmann-Voos S, Schnurch H, Martinez R, Moller N, Risau W, Ullrich A (1993) High affinity VEGF binding and developmental expression suggest flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72:835–846
Millauer B, Shawver LK, Plate KH, Risau W, Ullrich A (1994) Glioblastoma growth inhibited in vivo by a dominantnegative Flk-1 mutant. Nature 367:576–579
Miller JW, Adamis AP, Shima DT, D'Amore PA, Moulton RS, O'Reilly MS, Folkman J, Dvorak HF, Brown LF, Berse B, et al (1994) Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am J Pathol 145:574–584
Minchenko A, Bauer T, Salceda S, Caro J (1994) Hypoxic stimulation of vascular endothelial growth factor expression in vitro and in vivo. Lab Invest 71:374–379
Moghaddam A, Bicknell R (1992) Expression of platelet-derived endothelial growth factor in Escherichia coli and confirmation of its thymidine phosphorylase activity. Biochemistry 31:12141–12146
Montesano R (1992) 1992 Mack Forster Award Lecture. Review. Regulation of angiogenesis in vitro. Eur J Clin Invest 22:504–515
Montrucchio G, Lupia E, Battaglia E, Passerini G, Bussolino F, Emanuelli G, Camussi G (1994) Tumor necrosis factor α-induced angiogenesis depends on in situ platelet-activating factor biosynthesis. J Exp Med 180:377–382
Moses MA (1993) A cartilage-derived inhibitor of neovascularization and metalloproteinases. Clin Exp Rheumatol 11 [Suppl] 8:S67-S69
Müller G, Behrens J, Nussbaumer P, Bohler P, Birchmaier W (1987) Inhibitory action of transforming growth factor β on endothelial cells. Proc Natl Acad Sci USA 84:5600–5604
Nguyen M, Strubel NA, Bischoff J (1993) A role for sialyl Lewis-X/A glycoconjugates in capillary morphogenesis. Nature 365:267–269
Nguyen NM, Lehr JE, Pienta KJ (1993) Pentosan inhibits angiogenesis in vitro and suppresses prostate tumor growth in vivo. Anticancer. Res 13:2143–2147
Nguyen M, Watanabe H, Budson AE, Richie JP, Hayes DF, Folkman J (1994) Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. J Natl Cancer Inst. 86:356–361
Nicosia RF, Villaschi S, Smith M (1994) Isolation and characterization of vasoformative endothelial cells from the rat aorta. In Vitro Cell Develop Biol 30A:394–399
O'Brien KD, Allen MD, McDonald TO, Chait A, Harlan JM, Fishbein D, McCarty J, Ferguson M, Hudkins K, Benjamin CD, et al (1993) Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. Implications for the mode of progression of advanced coronary atherosclerosis. J Clin Invest 92:945–951
O'Rahilly R, Müller F (1992) The cardiovascular and lymphatic systems. In: O'Rahilly R, Müller F (eds) Human embryology and teratology. Wiley-Liss, New York, pp 107–138
O'Reilly MA, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, J Folkman (1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a lewis lung carcinoma. Cell 79:315–328
Oikawa T, Okayasu I, Ashino H, Morita I, Murota S, Shudo K (1993) Three novel synthetic retinoids, Re 80, Am 580 and Am 80, all exhibit anti-angiogenic activity in vivo. Eur J Pharmacol 249:113–116
Oliver SJ, Banquerigo ML, Brahn E (1994) Supression of collagen-induced arthritis using an angiogenesis inhibitor, AGM-1470, and microtubule stabilizer taxol Cell Immunol 157:291–299
Page C, Rose M, Yacoub M, Pigott R (1992) Antigenic heterogeneity of vascular endothelium. Am J Pathol 141:673–683
Park JE, Chen HH, Winer J, Houck KA, Ferrara N (1994) Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem 41:25646–25654
Passaniti A, Taylor RM, Pili R, Guo Y, Long PV, Haney JA, Pauly RR, Grant DS, Martin GR (1992) A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor. Lab Invest 67:519–528
Pepper MS, Ferrara N, Orci L, Montesano R (1991) Vascular endothelial growth factor (VEGF) induces plasminogen activators and plasminogen activator inhibitor-1 in microvascular endothelial cells. Biochem Biophys Res Commun 181:902–906
Pepper MS, Vassalli JD, Orci L, Montesano R (1993) Biphasic effect of transforming growth factor-β1 on in vitro angiogenesis. Exp Cell Res 204:356–363
Pepper MS, Wasi S, Ferrara N, Orci L, Montesano R (1994) In vitro angiogenic and proteolytic properties of bovine lymphatic endothelial cells. Exp Cell Res 210:298–305
Pierce GF, Tarpley JE, Yanagihara D, Mustoe TA, Fox GM, Thomason A (1992) Platelet-derived growth factor (BB homodimer), transforming growth factor-beta 1, and basic fibroblast growth factor in dermal wound healing. Neovessel and matrix formation and cessation of repair. Am J Pathol 140:1375–1388
Plate KH, Breier G, Farrell CL, Risau W (1992) Platelet-derived growth factor receptor-β is induced during tumor development and upregulated during tumor progression in endothelial cells in human gliomas. Lab Invest 67:529–534
Plate KH, Breier G, Weich HA, Risau W (1992) Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359:845–848
Plate KH, Breier G, Millauer B, Ullrich A, Risau W (1993) Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. Cancer Res 53:5822–5827
Pu LQ, Sniderman AD, Brassard R, Lachapelle KJ, Graham AM, Lisbona R, Symes JF (1993) Enhanced revascularization of the ischemic limb by angiogenic therapy. Circulation 88:208–215
Quyyumi AA, Diodati JG, Lakatos E, Bonow RO, Epstein SE (1993) Angiogenic effects of low molecular weight heparin in patients with stable coronary artery disease: a pilot study. J Am Coll Cardiol 22:635–641
Raines EW, Lane TF, Iruela-Arispe ML, Ross R, Sage EH (1992) The extracellular glycoprotein SPARC interacts with plateletderived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors. Proc Natl Acad Sci USA 89:1281–1285
Rastinejad F, Polverini PJ, Bouck NP (1989) Regulation of the activity of a novel inhibitor of angiogenesis by a cancer suppressor gene. Cell 56:345–355
Ravindranath N, Little-Ihrig L, Philips HS, Ferrara N, Zeleznik A (1992) Vascular endothelial factor messenger ribonucleic acid expression in the primate ovary. Endocrinology 131:254–260
Reuterdahl C, Sundberg C, Rubin K, Funa K, Gerdin B (1993) Tissue localization of beta receptors for platelet-derived growth factor and platelet-derived growth factor B chain during wound repair in humans. J Clin Invest 91:2065–2075
Reynolds LP, Killilea SD, Redmer DA (1992) Angiogenesis in the female reproductive system. FASEB J 6:886–892
Risau W (1990) Angiogenic growth factors. Prog Growth Factor Res 2:71–79
Risau W (1991) Embryonic angiogenesis factors. Pharmacol Ther 51:371–376
Risau W (1994) Angiogenesis and endothelial cell function. Arzneimittelforschung 44:416–417
Risau W, Drexler H, Mironov V, Smits A, Siegbahn A, Funa K, Heldin C (1992) Platelet-derived growth factor is angiogenic in vivo. Growth Factors 7:261–266
Robson MC, Phillips LG, Thomason A, Robson LE, Pierce GF (1992) Platelet-derived growth factor BB for the treatment of chronic pressure ulcers. Lancet 339:23–25
Rosen EM, Zitnik RJ, Elias JA, Bhargava MM, Wines J, Goldberg ID (1993) The interaction of HGF-SF with other cytokines in tumor invasion and angiogenesis. EXS 65:301–310
Rupnik MA, Carey A, Williams SK (1988) Phenotypic diversity in cultured cerebral microvascular endothelial cells. In Vitro Cell Develop Biol 24:435–444
Sabri MN, DiSciascio G, Cowley MJ, Alpert D, Vetrovec GW (1991) Coronary collateral recruitment: functional significance and relation to rate of vessel closure. Am Heart J 121:876–880
Sakuda H, Nakashima Y, Kuriyama S, Sueishi K (1992) Media conditioned by smooth muscle cells cultured in a variety of hypoxic environments stimulates in vitro angiogenesis. A relationship to transforming growth factor-β1. Am J Pathol 141:1507–1516
Sasayama S, Fujita M (1992) Recent insights into coronary collateral circulation. Circulation. 85:1197–1204
Sato Y, Rifkin DB (1989) Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-β1-like molecule by plasmin during co-culture. J Cell Biol 109:309–315
Schaper W, Gorge G, Winkler B, Schaper J (1988) The collateral circulation of the heart. Prog Cardiovasc Dis 31:57–77
Schaper W, Sharma HS, Quinkler W, Markert T, Wünsch M, Scharper J (1990) Molecular biologic concepts of coronary anastomoses. J Am Coll Cardiol 15:513–518
Schott RJ, Morrow LA (1993) Growth factors and angiogenesis. Cardiovasc Res 27:1155–1161
Schultz-Cherry S, Lawler J, Murphy-Ullrich JE (1994) The type 1 repeats of thrombospondin 1 activate latent transforming growth factor-β. J Biol Chem. 269:26783–26788
Schultz-Cherry S, Ribeiro S, Gentry L, Murphy-Ullrich JE (1994) Thrombospondin binds and activates the small and large forms of latent transforming growth factor-β in a chemically defined system. J Biol Chem 269:26775–26782
Shweiki D, Itin A, Soffer D, Keshet E (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843–845
Shweiki D, Itin A, Neufeld G, Gitay-Goren H, Keshet E (1993) Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. J Clin Invest 91:2235–2243
Smith DR, Polverini PJ, Kunkel SL, Orringer MB, Whyte R, Burdick MD, Wilke CA, Strieter RM (1994) Inhibition of interleukin 8 attenuates angiogenesis in bronchogenic carcinoma. J Exp Med 179:1409–1415
Smits A, Hermansson M, Nister M, Karnushina I, Heldin CH, Westermark B, Funa K (1989) Rat brain capillary endothelial cells express functional PDGF B-type receptors. Growth Factors 2:1–8
Soyombo AA, DiCorleto PE (1994) Stable expression of human platelet-derived growth factor B chain by bovine aortic endothelial cells. Matrix association and selective proteolytic cleavage by thrombin. J Biol Chem 269:17734–17740
Srivastava A, Laidler P, Davies RP, Horgan K, Hughes LE (1988) The prognostic significance of tumor vascularity in intermediate-thickness (0.76–4.0 mm thick) skin melanoma. Am J Pathol 133:419–423
Strieter RM, Kunkel SL, Elner VM, Martonyi CL, Koch AE, Polverini PJ, Elner S (1992) Interleukin-8. A corneal factor that induces neovascularization. Am J Pathol 141:1279–1284
Sueishi K, Kumamoto M, Sakuda H, Tanaka K (1993) Angiogenic processes in the pathogenesis of human coronary atherosclerosis. Curr Top Pathol 87:47–58
Taipale J, Koli K, Keski Oja J (1992) Release of transforming growth factor-beta 1 from the pericellular matrix of cultured fibroblasts and fibrosarcoma cells by plasmin and thrombin. J Biol Chem 267:25378–25384
Taipale J, Miyazono K, Heldin CH, Keski Oja J (1994) Latent transforming growth factor-β1 associates to fibroblast extracellular matrix via latent TGF-β binding protein. J Cell Biol 124:171–181
Takeshita S, Zheng LP, Brogi E, Kearney M, Pu LQ, Bunting S, Ferrara N, Symes JF, Isner JM (1994) Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. J Clin Invest 93:662–670
Tanaka H, Sukhova GK, Libby P (1994) Interaction of the allogeneic state and hypercholesterolemia in arterial lesion foration in experimental cardiac allografts. Arterioscler Thromb 14:734–745
Teicher BA, Holden SA, Ara G, Northey D (1993) Response of the FSaII fibrosarcoma to antiangiogenic modulators plus cytotoxic agents. Anticancer Res 13:2101–2106
Tolsma SS, Volpert OV, Good DJ, Frazier WA, Polverini PJ, Bouck N (1993) Peptides derived from two separate domains of the matrix protein thrombospondin-1 have anti-angiogenic activity. J Cell Biol 122:497–511
Tomoike H, Inou T, Watanabe K, Mizukami M, Kikuchi Y, Nakamura M (1983) Functional significance of collaterals during ameroid-induced coronary stenosis in conscious dogs. Circulation. 67:1001–1008
Unemori EN, Ferrara N, Bauer EA, Amento E (1992) Vascular endothelial growth factor induces interstitial collagenase expression in human endothelial cells. J Cell Physiol 153:557–562
Van Meir EG, Polverini PJ, Chazin VR, Huang SHJ, de Tribolet N, Cavenee WK (1994) Release of an inhibitor of angiogenesis upon induction of wild type p53 expression in glioblastoma cells. Nature Genetics 8:171–176
Vernon RB, Angello JC, Iruela Arispe ML, Lane TF, Sage EH (1992) Reorganization of basement membrane matrices by cellular traction promotes the formation of cellular networks in vitro. Lab Invest 66:536–547
Vukicevic S, Kleinman HK, Luyten FP, Roberts AB, Roche NS, Reddi AH (1992) Identification of multiple active growth factors in basement membrane Matrigel suggests caution in interpretation of cellular activity related to extracellular matrix components. Exp Cell Res 202:1–8
Wakui S, Furusato M, Itoh T, Sasaki H, Akiyama A, Kinoshita I, Asano K, Tokuda T, Aizawa S, Ushigome S (1992) Tumor angiogenesis in prostatic carcinoma with and without bone metastasis; a morphometric study. Am J Pathol 168:257–262
Weidner N (1993) Tumor angiogenesis: review of current applications in tumor prognostication. Semin Diagn Pathol 10:302–313
Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med 324:1–8
Weindel K, Marmé D, Weich HA (1992) AIDS-associated Kaposi's sarcoma cells in culture express vascular endothelial growth factor. Biochem Biophys Res Commun 183:1167–1174
Weinstat-Saslow D, Steeg PS (1994) Angiogenesis and colonization in the tumor metastatic process: basic and applied advances. FASEB J 8:401–407
White CW, Wolf SJ, Korones DN, Sondheimer HM, Tosi MF, Yu A (1991) Treatment of childhood angiomatous diseases with recombinant interferon-2a. J Ped 118:59–66
Wolfe MM, Bynum TE, Parsons WG, Malone KM, Szabo S, Folkman J (1994) Safety and efficacy of an angiogenic peptide, basic fibroblast growth factor (bFGF) in the treatment of gastroduodenal ulcers: a preliminary report. Gastroenterology 106:A212
Yanagisawa-Miwa A, Uchida Y, Nakamura F, Tomaru T, Kido H, Kamijo T, Sugimoto T, Kaji K, Utsuyama M, Kurashima C, et al (1992) Salvage of infarcted myocardium by angiogenic action of basic fibroblast growth factor. Science 257:1401–1403
Zhang Y, Cliff WJ, Schoefl GI, Higgins G (1993) Immunohistochemical study of intimal microvessels in coronary atherosclerosis. Am J Pathol 143:164–172
Ziche M, Morbidelli L, Alessandri G, Gullino P (1992) Angiogenesis can be stimulated or repressed in vivo by a change in GM3∶GD3 ganglioside ratio. Lab Invest 67:711–715
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Battegay, E.J. Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects. J Mol Med 73, 333–346 (1995). https://doi.org/10.1007/BF00192885
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00192885