Comparative Angiogenesis-Related Pathologies in Humans, Dogs, and Cats:
Mechanisms, Biomarkers, and Therapeutic Perspectives
DOI:
https://doi.org/10.22456/1679-9216.153432Keywords:
Angiogenesis, Comparative pathology, VEGF, Companion animals, Tumor microenvironment, One HealthAbstract
Background: Angiogenesis is a tightly regulated biological process essential for embryonic development, tissue repair, and vascular homeostasis. Dysregulated angiogenesis contributes to numerous pathological conditions, including cancer, retinal disorders, chronic inflammatory diseases, and ischemic injury. Although angiogenic mechanisms have been extensively characterized in humans, comparative information in companion animals remains fragmented despite the increasing clinical importance of angiogenesis in veterinary oncology, ophthalmology, and internal medicine. This review aimed to provide a comprehensive comparative synthesis of angiogenesis-related diseases in humans, dogs, and cats, emphasizing conserved and species-specific molecular pathways, biomarkers, diagnostic approaches, therapeutic strategies, and translational significance within the One Health framework.
Review: This review summarizes the physiological regulation of angiogenesis and compares major molecular mediators, including VEGF, FGF, angiopoietins, PDGF, HIF-1α, matrix metalloproteinases, and endothelial-pericyte interactions across species. Comparative evidence demonstrates that VEGF-centered signaling is highly conserved in humans, dogs, and cats, whereas important interspecies differences exist in gene expression, receptor activity, vascular architecture, biomarker availability, and therapeutic responses. Tumor-associated angiogenesis is examined using human solid cancers, canine hemangiosarcoma, and canine and feline mammary tumors as representative models, highlighting common mechanisms of hypoxia-driven vascular remodeling while emphasizing species-specific pathological characteristics. Ocular angiogenic disorders, including diabetic retinopathy, age-related macular degeneration, hypertensive retinopathy, progressive retinal atrophy, and retinal inflammatory diseases, are discussed from comparative anatomical and translational perspectives. The review further evaluates inflammatory and ischemic angiogenesis in rheumatoid arthritis, inflammatory bowel disease, myocardial ischemia, feline chronic gingivostomatitis, chronic enteropathies, and wound healing. Current angiogenesis-related biomarkers, including VEGF, angiopoietins, soluble VEGF receptors, and HIF-1α, together with immunohistochemistry, ELISA, molecular techniques, OCT/OCT-A, Doppler ultrasonography, and contrast-enhanced ultrasound, are critically compared regarding their diagnostic utility and limitations in veterinary medicine. Human anti-angiogenic therapies, including bevacizumab, ranibizumab, aflibercept, and tyrosine kinase inhibitors, are contrasted with current veterinary applications such as toceranib phosphate and emerging experimental approaches. Remaining challenges include limited species-specific reagents, insufficient biomarker validation, lack of standardized diagnostic protocols, restricted clinical trial infrastructure, and the need for expanded canine and feline omics resources.
Discussion: Comparative evaluation demonstrates that companion animals naturally develop angiogenesis-associated diseases closely resembling human disorders, supporting their value as translational models. However, meaningful species-specific biological differences preclude direct extrapolation of human data to veterinary medicine and underscore the necessity for dedicated veterinary investigations. Future progress will depend on the development of species-specific diagnostic reagents, integrated multi-omics analyses, advanced imaging technologies, collaborative clinical studies, and One Health research networks. Strengthening comparative angiogenesis research will improve diagnostic precision, facilitate the development of novel therapeutic strategies, and accelerate bidirectional translation between human and veterinary medicine.
Keywords: angiogenesis, comparative pathology, VEGF, companion animals, tumor microenvironment, One Health.
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1 Abramoff M.D., Fort P.E., Han I.C., Jayasundera K.T., Sohn E.H. & Gardner T.W. 2018. Approach for a Clinically Useful Comprehensive Classification of Vascular and Neural Aspects of Diabetic Retinal Disease. Investigative Ophthalmology & Visual Science. 59(1): 519-527. DOI: 10.1167/iovs.17-21873.
2 Asahara T., Chen D., Takahashi T., Fujikawa K., Kearney M., Magner M., Yancopoulos G.D. & Isner J.M. 1998. Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization. Circulation Research. 83(3): 233-240. DOI: 10.1161/01.RES.83.3.233.
3 Banzato T., Rubini G., Orlandi R., Bargellini P., Bonsembiante F. & Zotti A. 2020. Contrast-enhanced ultrasound features of hepatocellular carcinoma in dogs. Veterinary Record. 186(6): 187. DOI: 10.1136/vr.105282.
4 Bernabe L.F., Portela R., Nguyen S., Kisseberth W.C., Pennell M., Yancey M.F. & London C.A. 2013. Evaluation of the adverse event profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose. BMC Veterinary Research. 9: 190. DOI: 10.1186/1746-6148-9-190.
5 Bordeaux J., Welsh A., Agarwal S., Killiam E., Baquero M., Hanna J., Anagnostou V. & Rimm D.L. 2010. Antibody validation. BioTechniques. 48(3): 197-209. DOI: 10.2144/000113382.
6 Breier G., Albrecht U., Sterrer S. & Risau W. 1992. Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development. 114(2): 521-532. DOI: 10.1242/dev.114.2.521.
7 Brown D.M., Kaiser P.K., Michels M., Soubrane G., Heier J.S., Kim R.Y., Sy J.P., Schneider S. & ANCHOR Study Group. 2006. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. New England Journal of Medicine. 355(14): 1432-1444. DOI: 10.1056/NEJMoa062655.
8 Cabral T., Mello L.G.M., Lima L.H., Polido J., Regatieri C.V., Belfort R. Jr. & Mahajan V.B. 2017. Retinal and choroidal angiogenesis: a review of new targets. International Journal of Retina and Vitreous. 3: 31. DOI: 10.1186/s40942-017-0084-9.
9 Campa C., Alivernini G., Bolletta E., Parodi M.B. & Perri P. 2016. Anti-VEGF Therapy for Retinal Vein Occlusions. Current Drug Targets. 17(3): 328-336. DOI: 10.2174/1573399811666150615151324.
10 Cane G., Ginouves A., Marchetti S., Busca R., Pouyssegur J., Berra E., Hofman P. & Vouret-Craviari V. 2010. HIF-1alpha mediates the induction of IL-8 and VEGF expression on infection with Afa/Dr diffusely adhering Escherichia coli and promotes EMT-like behaviour. Cellular Microbiology. 12(5): 640-653. DOI: 10.1111/j.1462-5822.2009.01422.x.
11 Carter J. 2019. Hypertensive ocular disease in cats: A guide to fundic lesions to facilitate early diagnosis. Journal of Feline Medicine and Surgery. 21(1): 35-45. DOI: 10.1177/1098612X18818668.
12 Chen B., Lin S.J., Li W.T., Chang H.W., Pang V.F., Chu P.Y., Lee C.C., Nakayama H., Wu C.H. & Jeng C.R. 2020. Expression of HIF-1alpha and VEGF in feline mammary gland carcinomas: association with pathological characteristics and clinical outcomes. BMC Veterinary Research. 16(1): 125. DOI: 10.1186/s12917-020-02338-y.
13 Cho M.L., Jung Y.O., Moon Y.M., Min S.Y., Yoon C.H., Lee S.H., Park S.H., Cho C.S., Jue D.M. & Kim H.Y. 2006. Interleukin-18 induces the production of vascular endothelial growth factor (VEGF) in rheumatoid arthritis synovial fibroblasts via AP-1-dependent pathways. Immunology Letters. 103(2): 159-166. DOI: 10.1016/j.imlet.2005.10.020.
14 Claesson-Welsh L. & Welsh M. 2013. VEGFA and tumour angiogenesis. Journal of Internal Medicine. 273(2): 114-127. DOI: 10.1111/joim.12019.
15 Clifford C.A., Hughes D., Beal M.W., Mackin A.J., Henry C.J., Shofer F.S. & Sorenmo K.U. 2001. Plasma vascular endothelial growth factor concentrations in healthy dogs and dogs with hemangiosarcoma. Journal of Veterinary Internal Medicine. 15(2): 131-135. DOI: 10.1111/j.1939-1676.2001.tb01244.x.
16 Crispin S.M. & Mould J.R. 2001. Systemic hypertensive disease and the feline fundus. Veterinary Ophthalmology. 4(2): 131-140. DOI: 10.1046/j.1463-5224.2001.00190.x.
17 de Carlo T.E., Romano A., Waheed N.K. & Duker J.S. 2015. A review of optical coherence tomography angiography [OCTA]. International Journal of Retina and Vitreous. 15(1): 5. DOI: 10.1186/s40942-015-0005-8.
18 Distler J.H., Hirth A., Kurowska-Stolarska M., Gay R.E., Gay S. & Distler O. 2003. Angiogenic and angiostatic factors in the molecular control of angiogenesis. The Quarterly Journal of Nuclear Medicine. 47(3): 149-161.
19 Dor Y. & Keshet E. 1997. Ischemia-driven angiogenesis. Trends in Cardiovascular Medicine. 7(8): 289-294. DOI: 10.1016/S1050-1738(97)00091-1.
20 Dragneva G., Korpisalo P. & Yla-Herttuala S. 2013. Promoting blood vessel growth in ischemic diseases: challenges in translating preclinical potential into clinical success. Disease Models & Mechanisms. 6(2): 312-322. DOI: 10.1242/dmm.010413.
21 Dredge K., Marriott J.B., Macdonald C.D., Man H.W., Chen R., Muller G.W., Stirling D. & Dalgleish A.G. 2002. Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects. British Journal of Cancer. 87(10): 1166-1172. DOI: 10.1038/sj.bjc.6600607.
22 Dulmovits B.M. & Herman I.M. 2012. Microvascular remodeling and wound healing: a role for pericytes. International Journal of Biochemistry & Cell Biology. 44(11): 1800-1812. DOI: 10.1016/j.biocel.2012.06.031.
23 Eussen B.G.M., Schaveling J., Dragt M.J. & Blomme R.J. 2017. Stimulating collaboration between human and veterinary health care professionals. BMC Veterinary Research. 13(1): 174. DOI: 10.1186/s12917-017-1072-x.
24 Ferrara N. & Kerbel R.S. 2005. Angiogenesis as a therapeutic target. Nature. 438(7070): 967-974. DOI: 10.1038/nature04483.
25 Fraser-Bell S., Symes R. & Vaze A. 2017. Hypertensive eye disease: a review. Clinical and Experimental Ophthalmology. 45(1): 45-53. DOI: 10.1111/ceo.12905.
26 Garcia J., Hurwitz H.I., Sandler A.B., Miles D., Coleman R.L., Deurloo R. & Chinot O.L. 2020. Bevacizumab [Avastin®] in cancer treatment: A review of 15 years of clinical experience and future outlook. Cancer Treatment Reviews. 86: 102017. DOI: 10.1016/j.ctrv.2020.102017.
27 Giuliano A. 2021. Companion Animal Model in Translational Oncology; Feline Oral Squamous Cell Carcinoma and Canine Oral Melanoma. Biology. 11(1): 54. DOI: 10.3390/biology11010054.
28 Gotink K.J. & Verheul H.M. 2010. Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action? Angiogenesis. 139(1): 1-14. DOI: 10.1007/s10456-009-9160-6.
29 Haibe Y., Kreidieh M., El Hajj H., Khalifeh I., Mukherji D., Temraz S. & Shamseddine A. 2020. Resistance Mechanisms to Anti-angiogenic Therapies in Cancer. Frontiers in Oncology. 10: 221. DOI: 10.3389/fonc.2020.00221.
30 Heaton C.M., Fernandes A.F.A., Jark P.C. & Pan X. 2020. Evaluation of toceranib for treatment of apocrine gland anal sac adenocarcinoma in dogs. Journal of Veterinary Internal Medicine. 34(2): 873-881. DOI: 10.1111/jvim.15706.
31 Heilmann R.M., Cranford S.M., Ambrus A., Grutzner N., Schellenberg S., Ruaux C.G., Suchodolski J.S. & Steiner J.M. 2016. Validation of an enzyme-linked immunosorbent assay (ELISA) for the measurement of canine S100A12. Veterinary Clinical Pathology. 45(1): 135-147. DOI: 10.1111/vcp.12320.
32 Hellstrom M., Kalen M., Lindahl P., Abramsson A. & Betsholtz C. 1999. Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development. 126(14): 3047-3055. DOI: 10.1242/dev.126.14.3047.
33 Hofmeister E.H., King J., Read M.R. & Budsberg S.C. 2007. Sample size and statistical power in the small-animal analgesia literature. Journal of Small Animal Practice. 48(2): 76-79. DOI: 10.1111/j.1748-5827.2006.00234.x.
34 Hurwitz H., Fehrenbacher L., Novotny W., Cartwright T., Hainsworth J., Heim W., Berlin J., Baron A., Griffing S., Holmgren E., Ferrara N., Fyfe G., Rogers B., Ross R. & Kabbinavar F. 2004. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New England Journal of Medicine. 350(23): 2335-2342. DOI: 10.1056/NEJMoa032691.
35 Izquierdo E., Canete J.D., Celis R., Santiago B., Usategui A., Sanmarti R., Del Rey M.J. & Pablos J.L. 2009. Immature blood vessels in rheumatoid synovium are selectively depleted in response to anti-TNF therapy. PLoS ONE. 4(12): e8131. DOI: 10.1371/journal.pone.0008131.
36 Jackson J.R., Minton J.A., Ho M.L., Wei N. & Winkler J.D. 1997. Expression of vascular endothelial growth factor in synovial fibroblasts is induced by hypoxia and interleukin 1beta. Journal of Rheumatology. 24(7): 1253-1259.
37 Javanmard S.H., Hasanpour Z., Abbaspoor Z., Naderian G.A. & Jahanmard M. 2012. Aqueous concentrations of VEGF and soluble VEGF receptor-1 in diabetic retinopathy patients. Journal of Research in Medical Sciences. 17(12): 1124-1127.
38 Jayson G.C., Hicklin D.J. & Ellis L.M. 2012. Antiangiogenic therapy—evolving view based on clinical trial results. Nature Reviews Clinical Oncology. 9(5): 297-303. DOI: 10.1038/nrclinonc.2012.8.
39 Jayson G.C., Kerbel R., Ellis L.M. & Harris A.L. 2016. Antiangiogenic therapy in oncology: current status and future directions. The Lancet. 388(10043): 518-529. DOI: 10.1016/S0140-6736(15)01088-0.
40 Jeong H.S., Yun J.H., Lee D.H., Lee E.H. & Cho C.H. 2019. Retinal pigment epithelium-derived transforming growth factor-beta2 inhibits the angiogenic response of endothelial cells by decreasing vascular endothelial growth factor receptor-2 expression. Journal of Cellular Physiology. 234(4): 3837-3849. DOI: 10.1002/jcp.27156.
41 Jingjing L., Srinivasan B., Bian X., Downey H.F. & Roque R.S. 2000. Vascular endothelial growth factor is increased following coronary artery occlusion in the dog heart. Molecular and Cellular Biochemistry. 214(1-2): 23-30. DOI: 10.1023/A:1007115502758.
42 Jo D.H., Yun J.H., Cho C.S., Kim J.H., Kim J.H. & Cho C.H. 2019. Interaction between microglia and retinal pigment epithelial cells determines the integrity of outer blood-retinal barrier in diabetic retinopathy. Glia. 67(2): 321-331. DOI: 10.1002/glia.23542.
43 Kato Y., Asano K., Mogi T., Kutara K., Teshima K., Edamura K., Tsumagari S., Hasegawa A. & Tanaka S. 2007. Clinical significance of circulating vascular endothelial growth factor in dogs with mammary gland tumors. Journal of Veterinary Medical Science. 69(1): 77-80. DOI: 10.1292/jvms.69.77.
44 Kaya A., Ciledag A., Gulbay B.E., Poyraz B.M., Celik G., Sen E., Savas H. & Savas I. 2004. The prognostic significance of vascular endothelial growth factor levels in sera of non-small cell lung cancer patients. Respiratory Medicine. 98(7): 632-636. DOI: 10.1016/j.rmed.2003.12.017.
45 Kiessling F., Morgenstern B. & Zhang C. 2007. Contrast agents and applications to assess tumor angiogenesis in vivo by magnetic resonance imaging. Current Medicinal Chemistry. 14(1): 77-91. DOI: 10.2174/092986707779313516.
46 Kodama A., Sakai H., Matsuura S., Murakami M., Murai A., Mori T., Maruo K., Kimura T., Masegi T. & Yanai T. 2009. Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes. BMC Cancer. 9: 363. DOI: 10.1186/1471-2407-9-363.
47 Komaromy A.M., Andrew S.E., Denis H.M., Brooks D.E. & Gelatt K.N. 2004. Hypertensive retinopathy and choroidopathy in a cat. Veterinary Ophthalmology. 7(1): 3-9. DOI: 10.1111/j.1463-5224.2004.04014.x.
48 Konig M., Nentwig A., Marti E., Mirkovitch J., Adamik K.N. & Schuller S. 2019. Evaluation of plasma angiopoietin-2 and vascular endothelial growth factor in healthy dogs and dogs with systemic inflammatory response syndrome or sepsis. Journal of Veterinary Internal Medicine. 33(2): 569-577. DOI: 10.1111/jvim.15369.
49 Kusuhara S., Fukushima Y., Ogura S., Inoue N. & Uemura A. 2018. Pathophysiology of Diabetic Retinopathy: The Old and the New. Diabetes and Metabolism Journal. 42(5): 364-376. DOI: 10.4093/dmj.2018.0182.
50 Lai A.K. & Lo A.C. 2013. Animal models of diabetic retinopathy: summary and comparison. Journal of Diabetes Research. 2013: 106594. DOI: 10.1155/2013/106594.
51 Lairmore M.D. & Khanna C. 2014. Naturally occurring diseases in animals: contributions to translational medicine. ILAR Journal. 55(1): 1-3. DOI: 10.1093/ilar/ilu012.
52 Li X.P., Yang X.Y., Biskup E., Zhou J., Li H.L., Wu Y.F., Chen M.L. & Xu F. 2015. Co-expression of CXCL8 and HIF-1alpha is associated with metastasis and poor prognosis in hepatocellular carcinoma. Oncotarget. 6(26): 22880-22889. DOI: 10.18632/oncotarget.4412.
53 Liang S., Gao Y., Liu Y., Qiu C., Chen Y. & Zhu S. 2019. Contrast-enhanced Ultrasound in evaluating of angiogenesis and tumor staging of nasopharyngeal carcinoma in nude mice. PLoS ONE. 14(8): e0221638. DOI: 10.1371/journal.pone.0221638.
54 Lin C., McGough R., Aswad B., Block J.A. & Terek R. 2004. Hypoxia induces HIF-1alpha and VEGF expression in chondrosarcoma cells and chondrocytes. Journal of Orthopaedic Research. 22(6): 1175-1181. DOI: 10.1016/j.orthres.2004.03.002.
55 Lin P.Y., Sung P.H., Chung S.Y., Hsu S.L., Chung W.J., Sheu J.J., Hsueh S.K., Chen K.H., Wu R.W. & Yip H.K. 2018. Hyperbaric Oxygen Therapy Enhanced Circulating Levels of Endothelial Progenitor Cells and Angiogenesis Biomarkers, Blood Flow, in Ischemic Areas in Patients with Peripheral Arterial Occlusive Disease. Journal of Clinical Medicine. 7(12): 548. DOI: 10.3390/jcm7120548.
56 Linta N., Pey P., Baron Toaldo M., Pietra M., Felici M., Bettini G., Cipone M. & Diana A. 2021. Contrast-enhanced ultrasonography in dogs with inflammatory bowel disease. Journal of Veterinary Internal Medicine. 35(5): 2167-2176. DOI: 10.1111/jvim.16202.
57 Liu J., Wang Y., Akamatsu Y., Lee C.C., Stetler R.A., Lawton M.T. & Yang G.Y. 2014. Vascular remodeling after ischemic stroke: mechanisms and therapeutic potentials. Progress in Neurobiology. 115: 138-156. DOI: 10.1016/j.pneurobio.2013.11.004.
58 Madewell B.R., Griffey S.M. & Munn R.J. 1992. Ultrastructure of canine vasoformative tumors. Journal of Vascular Research. 29(2): 50-55. DOI: 10.1159/000158932.
59 Maggio F., DeFrancesco T.C., Atkins C.E., Pizzirani S., Gilger B.C. & Davidson M.G. 2000. Ocular lesions associated with systemic hypertension in cats: 69 cases [1985-1998]. Journal of the American Veterinary Medical Association. 217(5): 695-702. DOI: 10.2460/javma.2000.217.695.
60 McCormack P.L. & Keam S.J. 2008. Bevacizumab: a review of its use in metastatic colorectal cancer. Drugs. 68(4): 487-506. DOI: 10.2165/00003495-200868040-00009.
61 McKeeman G.C., Ardill J.E., Caldwell C.M., Hunter A.J. & McClure N. 2004. Soluble vascular endothelial growth factor receptor-1 [sFlt-1] is increased throughout gestation in patients who develop preeclampsia. American Journal of Obstetrics and Gynecology. 191(4): 1240-1246. DOI: 10.1016/j.ajog.2004.03.004.
62 Melo S.R., Januario E.V., Zanuto E., Miranda B.C., Macedo T.R., Cogliati B. & Matera J.M. 2021. Immunohistochemical Expression of Vascular Endothelial Growth Factor as a Prognostic Marker for Canine Mast Cell Tumors. Topics in Companion Animal Medicine. 42: 100506. DOI: 10.1016/j.tcam.2020.100506.
63 Mizoguchi A. 2012. Animal models of inflammatory bowel disease. Progress in Molecular Biology and Translational Science. 105: 263-320. DOI: 10.1016/B978-0-12-394596-9.00009-3.
64 Muellerleile L.M., Buxbaum B., Nell B. & Fux D.A. 2019. In-vitro binding analysis of anti-human vascular endothelial growth factor antibodies bevacizumab and aflibercept with canine, feline, and equine vascular endothelial growth factor. Research in Veterinary Science. 124: 233-238. DOI: 10.1016/j.rvsc.2019.03.018.
65 Obchoei S., Wongkhan S., Wongkham C., Li M., Yao Q. & Chen C. 2009. Cyclophilin A: potential functions and therapeutic target for human cancer. Medical Science Monitor. 15(11): RA221-32. PMID: 19865066.
66 Occelli L.M., Pirie C.G. & Petersen-Jones S.M. 2022. Non-invasive optical coherence tomography angiography: A comparison with fluorescein and indocyanine green angiography in normal adult dogs and cats. Veterinary Ophthalmology. 25(Suppl. 1): 164-178. DOI: 10.1111/vop.12973.
67 Olfert I.M. & Birot O. 2011. Importance of anti-angiogenic factors in the regulation of skeletal muscle angiogenesis. Microcirculation. 18(4): 316-330. DOI: 10.1111/j.1549-8719.2011.00092.x.
68 Olivares A.M., Althoff K., Chen G.F., Wu S., Morrisson M.A., DeAngelis M.M. & Haider N. 2017. Animal Models of Diabetic Retinopathy. Current Diabetes Reports. 17(10): 93. DOI: 10.1007/s11892-017-0913-0.
69 Paoloni M.C. & Khanna C. 2007. Comparative oncology today. Veterinary Clinics of North America: Small Animal Practice. 37(6): 1023-1032. DOI: 10.1016/j.cvsm.2007.08.003.
70 Park S.W., Yun J.H., Kim J.H., Kim K.W., Cho C.H. & Kim J.H. 2014. Angiopoietin 2 induces pericyte apoptosis via alpha3beta1 integrin signaling in diabetic retinopathy. Diabetes. 63(9): 3057-3068. DOI: 10.2337/db13-1942.
71 Peach C.J., Mignone V.W., Arruda M.A., Alcobia D.C., Hill S.J., Kilpatrick L.E. & Woolard J. 2018. Molecular Pharmacology of VEGF-A Isoforms: Binding and Signalling at VEGFR2. International Journal of Molecular Sciences. 19(4): 1264. DOI: 10.3390/ijms19041264.
72 Pennesi M.E., Neuringer M. & Courtney R.J. 2012. Animal models of age related macular degeneration. Molecular Aspects of Medicine. 33(4): 487-509. DOI: 10.1016/j.mam.2012.06.003.
73 Peters L.M., Reding Graf T., Giori L., Mevissen M., Graf R. & Howard J. 2024. Development and validation of an ELISA to measure regenerating island-derived protein 3E in canine blood. Veterinary Clinical Pathology. 53(2): 261-272. DOI: 10.1111/vcp.13352.
74 Petersen-Jones S.M. 1998. A review of research to elucidate the causes of the generalized progressive retinal atrophies. Veterinary Journal. 155(1): 5-18. DOI: 10.1016/S1090-0233(98)80028-2.
75 Pimentel P.A.B., Giuliano A., Beczkowski P.M. & Horta R.D.S. 2023. Molecular Profile of Canine Hemangiosarcoma and Potential Novel Therapeutic Targets. Veterinary Sciences. 10(6): 387. DOI: 10.3390/vetsci10060387.
76 Porrello A., Cardelli P. & Spugnini E.P. 2006. Oncology of companion animals as a model for humans: an overview of tumor histotypes. Journal of Experimental and Clinical Cancer Research. 25(1): 97-105.
77 Quach H., Ritchie D., Stewart A.K., Neeson P., Harrison S., Smyth M.J. & Prince H.M. 2010. Mechanism of action of immunomodulatory drugs [IMiDs] in multiple myeloma. Leukemia. 24(1): 22-32. DOI: 10.1038/leu.2009.236.
78 Rodrigues-Jesus J., Canadas-Sousa A., Vilhena H. & Dias-Pereira P. 2025. Inside the Tumor: Decoding the Feline Mammary Tumor Microenvironment and Its Prognostic Value-A Review. Veterinary Sciences. 12(10). DOI: 10.3390/vetsci12100959.
79 Rosenfeld P.J., Brown D.M., Heier J.S., Boyer D.S., Kaiser P.K., Chung C.Y., Kim R.Y. & MARINA Study Group. 2006. Ranibizumab for neovascular age-related macular degeneration. New England Journal of Medicine. 355(14): 1419-1431. DOI: 10.1056/NEJMoa054481.
80 Ruan Y., Jiang S. & Gericke A. 2021. Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels. International Journal of Molecular Sciences. 22(3). DOI: 10.3390/ijms22031296.
81 Rundhaug J.E. 2005. Matrix metalloproteinases and angiogenesis. Journal of Cellular and Molecular Medicine. 9(2): 267-285. DOI: 10.1111/j.1582-4934.2005.tb00355.x.
82 Ryu S., Lee J.H. & Kim S.I. 2006. IL-17 increased the production of vascular endothelial growth factor in rheumatoid arthritis synoviocytes. Clinical Rheumatology. 25(1): 16-20. DOI: 10.1007/s10067-005-1081-1.
83 Salven P., Ruotsalainen T., Mattson K. & Joensuu H. 1998. High pre-treatment serum level of vascular endothelial growth factor (VEGF) is associated with poor outcome in small-cell lung cancer. International Journal of Cancer. 79(2): 144-146. DOI: 10.1002/(SICI)1097-0215(19980417)79:2<144::AID-IJC8>3.0.CO;2-T.
84 Sarli G., Sassi F., Brunetti B., Rizzo A., Diracca L. & Benazzi C. 2007. Lymphatic vessels assessment in feline mammary tumours. BMC Cancer. 7: 7. DOI: 10.1186/1471-2407-7-7.
85 Scaldaferri F., Vetrano S., Sans M., Arena V., Straface G., Stigliano E., Repici A., Sturm A., Malesci A., Panes J., Yla-Herttuala S., Fiocchi C. & Danese S. 2009. VEGF-A links angiogenesis and inflammation in inflammatory bowel disease pathogenesis. Gastroenterology. 136(2): 585-595.e5. DOI: 10.1053/j.gastro.2008.09.064.
86 Scharf V.F., Farese J.P., Coomer A.R., Milner R.J., Taylor D.P., Salute M.E., Chang M.N., Neal D. & Siemann D.W. 2013. Effect of bevacizumab on angiogenesis and growth of canine osteosarcoma cells xenografted in athymic mice. American Journal of Veterinary Research. 74(5): 771-778. DOI: 10.2460/ajvr.74.5.771.
87 Seghezzi G., Patel S., Ren C.J., Gualandris A., Pintucci G., Robbins E.S., Shapiro R.L., Galloway A.C., Rifkin D.B. & Mignatti P. 1998. Fibroblast growth factor-2 [FGF-2] induces vascular endothelial growth factor (VEGF) expression in the endothelial cells of forming capillaries: an autocrine mechanism contributing to angiogenesis. Journal of Cell Biology. 141(7): 1659-1673. DOI: 10.1083/jcb.141.7.1659.
88 Sequeira I., Pires M.D.A., Leitao J., Henriques J., Viegas C. & Requicha J. 2022. Feline Oral Squamous Cell Carcinoma: A Critical Review of Etiologic Factors. Veterinary Sciences. 9(10): DOI: 10.3390/vetsci9100558.
89 Shin J.I., Lim H.Y., Kim H.W., Seung B.J. & Sur J.H. 2015. Analysis of Hypoxia-Inducible Factor-1alpha Expression Relative to Other Key Factors in Malignant Canine Mammary Tumours. Journal of Comparative Pathology. 153(2-3): 101-110. DOI: 10.1016/j.jcpa.2015.05.004.
90 Stepien R.L. 2011. Feline systemic hypertension: Diagnosis and management. Journal of Feline Medicine and Surgery. 13(1): 35-43. DOI: 10.1016/j.jfms.2010.11.008.
91 Stroud C., Dmitriev I., Kashentseva E., Bryan J.N., Curiel D.T., Rindt H., Reinero C., Henry C.J., Bergman P.J., Mason N.J., Gnanandarajah J.S., Engiles J.B., Gray F., Laughlin D., Gaurnier-Hausser A., Wallecha A., Huebner M., Paterson Y., O'Connor D., Treml L.S., Stannard J.P., Cook J.L., Jacobs M., Wyckoff G.J., Likins L., Sabbagh U., Skaff A., Guloy A.S., Hays H.D., LeBlanc A.K., Coates J.R., Katz M.L., Lyons L.A., Johnson G.C., Johnson G.S., O'Brien D.P., Duan D., Calvet J.P., Gandolfi B., Baron D.A., Weiss M.L., Webster D.A., Karanu F.N., Robb E.J. & Harman R.J. 2016. A One Health overview, facilitating advances in comparative medicine and translational research. Clinical and Translational Medicine. 5(Suppl. 1): 26. DOI: 10.1186/s40169-016-0107-4.
92 Tanabe A., Kobayashi D., Maeda K., Taguchi M. & Sahara H. 2019. Angiogenesis-related gene expression profile in clinical cases of canine cancer. Veterinary Medicine and Science. 5(1): 19-29. DOI: 10.1002/vms3.127.
93 Taylor P.C. 2005. Serum vascular markers and vascular imaging in assessment of rheumatoid arthritis disease activity and response to therapy. Rheumatology. 44(6): 721-728. DOI: 10.1093/rheumatology/keh524.
94 Uludag G., Hassan M., Matsumiya W., Pham B.H., Chea S., Trong Tuong Than N., Doan H.L., Akhavanrezayat A., Halim M.S., Do D.V. & Nguyen Q.D. 2022. Efficacy and safety of intravitreal anti-VEGF therapy in diabetic retinopathy: what we have learned and what should we learn further? Expert Opinion on Biological Therapy. 22(10): 1275-1291. DOI: 10.1080/14712598.2022.2100694.
95 Vail D.M. & MacEwen E.G. 2000. Spontaneously occurring tumors of companion animals as models for human cancer. Cancer Investigation. 18(8): 781-792. DOI: 10.3109/07357900009012210.
96 Van Boxtel S.A. 2003. Hypertensive retinopathy in a cat. Canadian Veterinary Journal. 44(2): 147-149.
97 Vapniarsky N., Simpson D.L., Arzi B., Taechangam N., Walker N.J., Garrity C., Bulkeley E. & Borjesson D.L. 2020. Histological, Immunological, and Genetic Analysis of Feline Chronic Gingivostomatitis. Frontiers in Veterinary Science. 7: 310. DOI: 10.3389/fvets.2020.00310.
98 Viallard C. & Larrivee B. 2017. Tumor angiogenesis and vascular normalization: alternative therapeutic targets. Angiogenesis. 20(4): 409-426. DOI: 10.1007/s10456-017-9562-9.
99 Wei X., Chen Y., Jiang X., Peng M., Liu Y., Mo Y., Ren D., Hua Y., Yu B., Zhou Y., Liao Q., Wang H., Xiang B., Zhou M., Li X., Li G., Li Y., Xiong W. & Zeng Z. 2021. Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments. Molecular Cancer. 20(1): 7. DOI: 10.1186/s12943-020-01288-1.
100 Wergin M.C. & Kaser-Hotz B. 2004. Plasma vascular endothelial growth factor (VEGF) measured in seventy dogs with spontaneously occurring tumours. In Vivo. 18(1): 15-19.
101 Williams M. 2018. Reagent Validation to Facilitate Experimental Reproducibility. Current Protocols in Pharmacology. 81(1): e40. DOI: 10.1002/cpph.40.
102 Xiao Y., Wu M., Xu W., Sun S., Liu T., Liu Y., Li H., Feng N., Tu C. & Feng Y. 2025. Development and validation of a blocking ELISA for measurement of rabies virus neutralizing antibody. Journal of Clinical Microbiology. 63(6): e0204924. DOI: 10.1128/JCM.02049-24.
103 Yun J.H. 2021. Hepatocyte growth factor prevents pericyte loss in diabetic retinopathy. Microvascular Research. 133: 104103. DOI: 10.1016/j.mvr.2020.104103.
104 Yun J.H. 2021. Interleukin-1beta induces pericyte apoptosis via the NF-kappaB pathway in diabetic retinopathy. Biochemical and Biophysical Research Communications. 546: 46-53. DOI: 10.1016/j.bbrc.2021.01.108.
105 Yun J.H. 2025. Interleukin-4 prevents increased endothelial permeability by inducing pericyte survival and modulating microglial responses in diabetic retinopathy. Frontiers in Endocrinology. 16: 1609796. DOI: 10.3389/fendo.2025.1609796.
106 Yun J.H., Koh Y.J., Jeong H.S., Lee D.H., Lee E.H. & Cho C.H. 2018. Propranolol increases vascular permeability through pericyte apoptosis and exacerbates oxygen-induced retinopathy. Biochemical and Biophysical Research Communications. 503(4): 2792-2799. DOI: 10.1016/j.bbrc.2018.08.041.
107 Yun J.H., Lee D.H., Jeong H.S., Kim S.H., Ye S.K. & Cho C.H. 2022. STAT3 activation in microglia increases pericyte apoptosis in diabetic retinas through TNF-alpha/AKT/p70S6 kinase signaling. Biochemical and Biophysical Research Communications. 613: 133-139. DOI: 10.1016/j.bbrc.2022.05.004.
108 Yun J.H., Lee H.M., Lee E.H., Park J.W. & Cho C.H. 2013. Hypoxia reduces endothelial Ang1-induced Tie2 activity in a Tie1-dependent manner. Biochemical and Biophysical Research Communications. 436(4): 691-697. DOI: 10.1016/j.bbrc.2013.06.018.
109 Yun J.H., Park S.W., Kim K.J., Bae J.S., Lee E.H., Paek S.H., Kim S.U., Ye S.K., Kim J.H. & Cho C.H. 2017. Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy. Journal of Cellular Physiology. 232(5): 1123-1134. DOI: 10.1002/jcp.25575.
110 Zappulli V., Rasotto R., Caliari D., Mainenti M., Pena L., Goldschmidt M.H. & Kiupel M. 2015. Prognostic evaluation of feline mammary carcinomas: a review of the literature. Veterinary Pathology. 52(1): 46-60. DOI: 10.1177/0300985814528221.
111 Zeiss C.J. 2013. Translational models of ocular disease. Veterinary Ophthalmology. 16(Suppl. 1): 15-33. DOI: 10.1111/vop.12065.
112 Zhang Y., Wang H., Oliveira R.H.M., Zhao C. & Popel A.S. 2022. Systems biology of angiogenesis signaling: Computational models and omics. WIREs Mechanisms of Disease. 14(4): e1550. DOI: 10.1002/wsbm.1550.
113 Zheng J., Chen P., Zhong J., Cheng Y., Chen H., He Y. & Chen C. 2021. HIF-1alpha in myocardial ischemia-reperfusion injury [Review]. Molecular Medicine Reports. 23(5): DOI: 10.3892/mmr.2021.11991.
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