Peripheral vascular disease: preclinical models and emerging therapeutic targeting of the vascular endothelial growth factor ligand-receptor system

References

• Chung AS, Ferrara N. Developmental and pathological angiogenesis. Annu Rev Cell Dev Biol. 2011;27:563–584.
   PubMed Web of Science ®Google Scholar
• Dragneva G, Korpisalo P, Yla-Herttuala S. Promoting blood vessel growth in ischemic diseases: challenges in translating preclinical potential into clinical success. Dis Model Mech. 2013 Mar;6(2):312–322.
   PubMed Web of Science ®Google Scholar
• De Palma M, Biziato D, Petrova TV. Microenvironmental regulation of tumour angiogenesis. Nat Rev Cancer. 2017 Aug;17(8):457–474.
   PubMed Web of Science ®Google Scholar
• Ribatti D. Judah Folkman, a pioneer in the study of angiogenesis. Angiogenesis. 2008;11(1):3–10.
   PubMed Web of Science ®Google Scholar
• Vincent KA, Jiang C, Boltje I, et al. Gene therapy progress and prospects: therapeutic angiogenesis for ischemic cardiovascular disease. Gene Ther. 2007 May;14(10):781–789.
   PubMed Web of Science ®Google Scholar
• Freedman SB, Isner JM. Therapeutic angiogenesis for ischemic cardiovascular disease. J Mol Cell Cardiol. 2001 Mar;33(3):379–393.
   PubMed Web of Science ®Google Scholar
• Khan KA, Kerbel RS. Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa. Nat Rev Clin Oncol. 2018 May;15(5):310–324.
   PubMed Web of Science ®Google Scholar
• Harry LE, Paleolog EM. From the cradle to the clinic: VEGF in developmental, physiological, and pathological angiogenesis. Birth Defects Res C Embryo Today. 2003 Nov;69(4):363–374.
   PubMedGoogle Scholar
• Ferrara N. The role of VEGF in the regulation of physiological and pathological angiogenesis. EXS. 2005;94:209–231. DOI:10.1007/3-7643-7311-3_15.
   PubMedGoogle Scholar
• Arcondeguy T, Lacazette E, Millevoi S, et al. VEGF-A mRNA processing, stability and translation: a paradigm for intricate regulation of gene expression at the post-transcriptional level. Nucleic Acids Res. 2013 Sep;41(17):7997–8010.
   PubMed Web of Science ®Google Scholar
• Vitt UA, Hsu SY, Hsueh AJW. Evolution and classification of cystine knot-containing hormones and related extracellular signaling molecules. Mol Endocrinol. 2001 May;15(5):681–694.
   PubMedGoogle Scholar
• Gong BW, Liang D, Chew TG, et al. Characterization of the zebrafish vascular endothelial growth factor A gene: comparison with vegf-A genes in mammals and Fugu. Biochimica et Biophysica Acta-Gene Struct Expression. 2004 Jan 5;1676(1):33–40.
   PubMedGoogle Scholar
• Tammela T, Enholm B, Alitalo K, et al. The biology of vascular endothelial growth factors. Cardiovasc Res. 2005 Feb 15;65(3):550–563.
   PubMed Web of Science ®Google Scholar
• Shibuya M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti- and pro-angiogenic therapies. Genes Cancer. 2011 Dec;2(12):1097–1105.
   PubMedGoogle Scholar
• Abhinand CS, Raju R, Soumya SJ, et al. VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis. J Cell Commun Signal. 2016 Dec;10(4):347–354.
   PubMed Web of Science ®Google Scholar
• Kaipainen A, Korhonen J, Mustonen T, et al. Expression of the Fms-Like tyrosine kinase-4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3566–3570.
   PubMed Web of Science ®Google Scholar
• Ceci C, Atzori MG, Lacal PM, et al. Role of VEGFs/VEGFR-1 signaling and its inhibition in modulating tumor invasion: experimental evidence in different metastatic cancer models. Int J Mol Sci. 2020 Feb 18;21:4.
   Web of Science ®Google Scholar
• Roberts DM, Kearney JB, Johnson JH, et al. The vascular endothelial growth factor (VEGF) receptor Flt-1 (VEGFR-1) modulates Flk-1 (VEGFR-2) signaling during blood vessel formation. Am J Pathol. 2004 May;164(5):1531–1535.
   PubMed Web of Science ®Google Scholar
• Annex BH. Therapeutic angiogenesis for critical limb ischaemia. Nat Rev Cardiol. 2013 Jul;10(7):387–396.
   PubMed Web of Science ®Google Scholar
• Zemaitis MR, Boll JM, Dreyer MA. Peripheral arterial disease. Treasure Island (FL): StatPearls; 2020.
   Google Scholar
• Levin SR, Arinze N, Siracuse JJ. Lower extremity critical limb ischemia: a review of clinical features and management. Trends Cardiovasc Med. 2020 Apr;30(3):125–130.
   PubMed Web of Science ®Google Scholar
• Pratt CM. Analysis of the cilostazol safety database. Am J Cardiol. 2001 Jun 28;87(12a):28d–33d.
   PubMed Web of Science ®Google Scholar
• Regensteiner JG, Ware JE Jr., McCarthy WJ, et al. Effect of cilostazol on treadmill walking, community-based walking ability, and health-related quality of life in patients with intermittent claudication due to peripheral arterial disease: meta-analysis of six randomized controlled trials. J Am Geriatr Soc. 2002 Dec;50(12):1939–1946.
   PubMed Web of Science ®Google Scholar
• Abbas R, Chow CP, Browder NJ, et al. In vitro metabolism and interaction of cilostazol with human hepatic cytochrome P450 isoforms. Hum Exp Toxicol. 2000 Mar;19(3):178–184.
   PubMed Web of Science ®Google Scholar
• Suri A, Bramer SL. Effect of omeprazole on the metabolism of cilostazol. Clin Pharmacokinet. 1999;37:53–59.
   PubMed Web of Science ®Google Scholar
• Giacca M, Zacchigna S. VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond. Gene Ther. 2012 Jun;19(6):622–629.
   PubMed Web of Science ®Google Scholar
• Makinen K, Manninen H, Hedman M, et al. Increased vascularity detected by digital subtraction angiography after VEGF gene transfer to human lower limb artery: a randomized, placebo-controlled, double-blinded phase II study. Mol Ther. 2002 Jul;6(1):127–133.
   PubMed Web of Science ®Google Scholar
• Kusumanto YH, van Weel V, Mulder NH, et al. Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: a double-blind randomized trial. Hum Gene Ther. 2006 Jun;17(6):683–691.
   PubMed Web of Science ®Google Scholar
• Baumgartner I, Pieczek A, Manor O, et al. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation. 1998 Mar 31;97(12):1114–1123.
   PubMed Web of Science ®Google Scholar
• Rasmussen HS, Rasmussen CS, Macko J. VEGF gene therapy for coronary artery disease and peripheral vascular disease. Cardiovasc Radiat Med. 2002 Apr-Jun;3(2):114–117.
   PubMedGoogle Scholar
• Rajagopalan S, Mohler E 3rd, Lederman RJ, et al. Regional angiogenesis with vascular endothelial growth factor (VEGF) in peripheral arterial disease: design of the RAVE trial. Am Heart J. 2003 Jun;145(6):1114–1118.
   PubMed Web of Science ®Google Scholar
• Rajagopalan S, Mohler ER 3rd, Lederman RJ, et al. Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication. Circulation. 2003 Oct 21;108(16):1933–1938.
   PubMed Web of Science ®Google Scholar
• Bates DO, Cui TG, Doughty JM, et al. VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma. Cancer Res. 2002 Jul 15;62(14):4123–4131.
   PubMed Web of Science ®Google Scholar
• Zirlik K, Duyster J. Anti-angiogenics: current situation and future perspectives. Oncol Res Treat. 2018;41(4):166–171.
   PubMed Web of Science ®Google Scholar
• Campa C, Harding SP. Anti-VEGF compounds in the treatment of neovascular age related macular degeneration. Curr Drug Targets. 2011 Feb;12(2):173–181.
   PubMed Web of Science ®Google Scholar
• Jazwa A, Florczyk U, Grochot-Przeczek A, et al. Limb ischemia and vessel regeneration: is there a role for VEGF? Vascul Pharmacol. 2016 Nov;86:18–30.
   PubMed Web of Science ®Google Scholar
• Rivard A, Silver M, Chen DF, et al. Rescue of diabetes-related impairment of angiogenesis by intramuscular gene therapy with adeno-VEGF. Am J Pathol. 1999 Feb;154(2):355–363.
   PubMed Web of Science ®Google Scholar
• Couffinhal T, Silver M, Kearney M, et al. Impaired collateral vessel development associated with reduced expression of vascular endothelial growth factor in ApoE(-/-) mice. Circulation. 1999 Jun 22;99(24):3188–3198.
   PubMed Web of Science ®Google Scholar
• Dai QS, Thompson MA, Pippen AM, et al. Alterations in endothelial cell proliferation and apoptosis contribute to vascular remodeling following hind-limb ischemia in rabbits. Vasc Med. 2002 May;7(2):87–91.
   PubMed Web of Science ®Google Scholar
• Dai QS, Huang JH, Klitzman B, et al. Engineered zinc finger-activating vascular endothelial growth factor transcription factor plasmid DNA induces therapeutic angiogenesis in rabbits with hindlimb ischemia. Circulation. 2004 Oct 19;110(16):2467–2475.
   PubMed Web of Science ®Google Scholar
• Xie DH, Li YJ, Reed EA, et al. An engineered vascular endothelial growth factor-activating transcription factor induces therapeutic angiogenesis in ApoE knockout mice with hindlimb ischemia. J Vasc Surg. 2006 Jul;44(1):166–175.
   PubMed Web of Science ®Google Scholar
• Li YJ, Hazarika S, Xie DH, et al. In mice with type 2 diabetes, a vascular endothelial growth factor (VEGF)-activating transcription factor modulates VEGF signaling and induces therapeutic angiogenesis after hindlimb ischemia. Diabetes. 2007 Mar;56(3):656–665.
   PubMed Web of Science ®Google Scholar
• Aref Z, De Vries MR, Quax PHA. Variations in surgical procedures for inducing hind limb ischemia in mice and the impact of these variations on neovascularization assessment. Int J Mol Sci. 2019 Aug;20(15). DOI:10.3390/ijms20153704.
   PubMed Web of Science ®Google Scholar
• Sealock R, Zhang H, Lucitti JL, et al. Congenic fine-mapping identifies a major causal locus for variation in the native collateral circulation and ischemic injury in brain and lower extremity. Circ Res. 2014 Feb 14;114(4):660–671.
   PubMed Web of Science ®Google Scholar
• Okeke E, Dokun AO. Role of genetics in peripheral arterial disease outcomes; significance of limb-salvage quantitative locus-1 genes. Exp Biol Med. 2018 Jan;243(2):190–197.
   Web of Science ®Google Scholar
• Md AOD, Keum S, Hazarika S, et al. A quantitative trait locus (LSq-1) on mouse chromosome 7 is linked to the absence of tissue loss after surgical Hindlimb ischemia. Circulation. 2008 Mar 4;117(9):1207–1215.
   PubMed Web of Science ®Google Scholar
• Krishna SM, Omer SM, Li JZ, et al. Development of a two-stage limb ischemia model to better simulate human peripheral artery disease. Sci Rep-Uk. 2020 Feb 26;10(1).
   Web of Science ®Google Scholar
• Ganta VC, Choi M, Kutateladze A, et al. VEGF165b modulates endothelial VEGFR1-STAT3 signaling pathway and angiogenesis in human and experimental peripheral arterial disease. Circ Res. 2017 Jan 20;120(2):282–295.
   PubMed Web of Science ®Google Scholar
• Kikuchi R, Nakamura K, MacLauchlan S, et al. An antiangiogenic isoform of VEGF-A contributes to impaired vascularization in peripheral artery disease. Nat Med. 2014 Dec;20(12):1464–1471.
   PubMed Web of Science ®Google Scholar
• Poltorak Z, Cohen T, Neufeld G. The VEGF splice variants: properties, receptors, and usage for the treatment of ischemic diseases. Herz. 2000 Mar;25(2):126–129.
   PubMed Web of Science ®Google Scholar
• Grunstein J, Masbad JJ, Hickey R, et al. Isoforms of vascular endothelial growth factor act in a coordinate fashion to recruit and expand tumor vasculature. Mol Cell Biol. 2000 Oct;20(19):7282–7291.
   PubMed Web of Science ®Google Scholar
• Park JE, Keller GA, Ferrara N. Vascular endothelial growth-factor (Vegf) isoforms - differential deposition into the subepithelial extracellular-matrix and bioactivity of extracellular matrix-bound vegf. Mol Biol Cell. 1993 Dec;4(12):1317–1326.
   PubMed Web of Science ®Google Scholar
• Bates DO, Mavrou A, Qiu Y, et al. Detection of VEGF-A(xxx)b isoforms in human tissues. PLoS One. 2013;8(7):e68399.
   PubMed Web of Science ®Google Scholar
• Woolard J, Wang WY, Bevan HS, et al. VEGF165b, an inhibitory vascular endothelial growth factor splice variant: mechanism of action, in vivo effect on angiogenesis and endogenous protein expression. Cancer Res. 2004 Nov 1;64(21):7822–7835.
   PubMed Web of Science ®Google Scholar
• Kawamura H, Li XJ, Harper SJ, et al. Vascular endothelial growth factor (VEGF)-A165b is a weak in vitro agonist for VEGF receptor-2 due to lack of coreceptor binding and deficient regulation of kinase activity. Cancer Res. 2008 Jun 15;68(12):4683–4692.
   PubMed Web of Science ®Google Scholar
• Catena R, Larzabal L, Larrayoz M, et al. VEGF(1)(2)(1)b and VEGF(1)(6)(5)b are weakly angiogenic isoforms of VEGF-A. Mol Cancer. 2010 Dec 31;9:320.
   PubMed Web of Science ®Google Scholar
• Harper SJ, Bates DO. VEGF-A splicing: the key to anti-angiogenic therapeutics? Nat Rev Cancer. 2008 Nov;8(11):880–887.
   PubMed Web of Science ®Google Scholar
• Waltenberger J, Claesson-Welsh L, Siegbahn A, et al. Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J Biol Chem. 1994 Oct 28;269(43):26988–26995.
   PubMed Web of Science ®Google Scholar
• Sawano A, Takahashi T, Yamaguchi S, et al. Flt-1 but not KDR/Flk-1 tyrosine kinase is a receptor for placenta growth factor, which is related to vascular endothelial growth factor. Cell Growth Differ. 1996 Feb;7(2):213–221.
   PubMedGoogle Scholar
• Shalaby F, Rossant J, Yamaguchi TP, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995 Jul 6;376(6535):62–66.
   PubMed Web of Science ®Google Scholar
• Fong GH, Rossant J, Gertsenstein M, et al. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature. 1995 Jul 6;376(6535):66–70.
   PubMed Web of Science ®Google Scholar
• Hiratsuka S, Minowa O, Kuno J, et al. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci USA. 1998 Aug 4;95(16):9349–9354.
   PubMed Web of Science ®Google Scholar
• Albonici L, Giganti MG, Modesti A, et al. Multifaceted role of the placental growth factor (PlGF) in the antitumor immune response and cancer progression. Int J Mol Sci. 2019 Jun 2;20:12.
   Web of Science ®Google Scholar
• Luttun A, Tjwa M, Carmeliet P. Placental growth factor (PlGF) and its receptor Flt-1 (VEGFR-1): novel therapeutic targets for angiogenic disorders. Ann N Y Acad Sci. 2002 Dec;979:80–93.
   PubMed Web of Science ®Google Scholar
• Lal N, Puri K, Rodrigues B. Vascular endothelial growth factor B and its signaling. Front Cardiovasc Med. 2018 Apr 20;5. DOI:10.3389/fcvm.2018.00039.
   PubMed Web of Science ®Google Scholar
• Cao RH, Xue Y, Hedlund EM, et al. VEGFR1-mediated pericyte ablation links VEGF and PlGF to cancer-associated retinopathy. Proc Natl Acad Sci USA. 2010 Jan 12;107(2):856–861.
   PubMed Web of Science ®Google Scholar
• Pipp F, Heil M, Issbrucker K, et al. VEGFR-1-selective VEGF homologue PlGF is arteriogenic - Evidence for a monocyte-mediated mechanism. Circ Res. 2003 Mar 7;92(4):378–385.
   PubMed Web of Science ®Google Scholar
• Boscolo E, Mulliken JB, Bischoff J. VEGFR-1 mediates endothelial differentiation and formation of blood vessels in a murine model of infantile hemangioma. Am J Pathol. 2011 Nov;179(5):2266–2277.
   PubMed Web of Science ®Google Scholar
• Robciuc MR, Kivela R, Williams IM, et al. VEGFB/VEGFR1-induced expansion of adipose vasculature counteracts obesity and related metabolic complications. Cell Metab. 2016 Apr 12;23(4):712–724.
   PubMed Web of Science ®Google Scholar
• Park K, Amano H, Ito Y, et al. Vascular endothelial growth factor receptor 1 (VEGFR1) tyrosine kinase signaling facilitates granulation tissue formation with recruitment of VEGFR1(+) cells from bone marrow. J Pharmacol Sci. 2016 Mar;130(3):S115–S115.
   Web of Science ®Google Scholar
• Amano H, Mastui Y, Ito Y, et al. The role of vascular endothelial growth factor receptor 1 tyrosine kinase signaling in bleomycin-induced pulmonary fibrosis. Biomed Pharmacother. 2019 Sep;117.
   Web of Science ®Google Scholar
• Murakami M, Zheng YJ, Hirashima M, et al. VEGFR1 tyrosine kinase signaling promotes lymphangiogenesis as well as angiogenesis indirectly via macrophage recruitment. Arteriosclerosis Thrombosis Vasc Biol. 2008 Apr;28(4):658–664.
   PubMed Web of Science ®Google Scholar
• Amano H, Kato S, Ito Y, et al. The role of vascular endothelial growth factor receptor-1 signaling in the recovery from ischemia. Plos One. 2015 Jul 2;10(7). DOI:10.1371/journal.pone.0131445.
   Web of Science ®Google Scholar
• Sselvaraj D, Gangadharan V, Michalski CW, et al. A functional role for VEGFR1 expressed in peripheral sensory neurons in cancer pain (vol 27, pg 780, 2015). Cancer Cell. 2015 Aug 10;28(2):270-270.
   Web of Science ®Google Scholar
• Yao J, Wu XM, Zhuang GL, et al. Expression of a functional VEGFR-1 in tumor cells is a major determinant of anti-PlGF antibodies efficacy. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11590–11595.
   PubMed Web of Science ®Google Scholar
• Sekiguchi K, Ito Y, Hattori K, et al. VEGF receptor 1-expressing macrophages recruited from bone marrow enhances angiogenesis in endometrial tissues. Sci Rep-Uk. 2019 May 7;9.
   Web of Science ®Google Scholar
• Lisi L, Ciotti GMP, Chiavari M, et al. Vascular endothelial growth factor receptor 1 in glioblastoma-associated microglia/macrophages. Oncol Rep. 2020 Jun;43(6):2083–2092.
   PubMed Web of Science ®Google Scholar
• Mosser DM, Hamidzadeh K, Goncalves R. Macrophages and the maintenance of homeostasis. Cell Mol Immunol. 2020 Sep 15:579–587.
   PubMed Web of Science ®Google Scholar
• Fung E, Helisch A. Macrophages in collateral arteriogenesis. Front Physiol. 2012;3. DOI:10.3389/fphys.2012.00353
   PubMed Web of Science ®Google Scholar
• Jetten N, Donners MMPC, Wagenaar A, et al. Local delivery of polarized macrophages improves reperfusion recovery in a mouse hind limb ischemia model. Plos One. 2013 Jul 24;8(7). DOI:10.1371/journal.pone.0068811.
   Web of Science ®Google Scholar
• Hong HL, Tian XY. The role of macrophages in vascular repair and regeneration after ischemic injury. Int J Mol Sci. 2020 Sep;21(17). DOI:10.3390/ijms21176328.
   Web of Science ®Google Scholar
• Gallagher KA. Recruitment and therapeutic application of macrophages in skeletal muscles after hind limb ischemia INVITED COMMENTARY. J Vasc Surg. 2018 Jun;67(6):1920-1920.
   PubMed Web of Science ®Google Scholar
• Ganta VC, Choi MH, Kutateladze A, et al. A MicroRNA93-interferon regulatory factor-9-immunoresponsive gene-1-Itaconic acid pathway modulates M2-like macrophage polarization to revascularize ischemic muscle. Circulation. 2017 Jun 13;135(24):2403-+.
   PubMed Web of Science ®Google Scholar
• Murray PJ. Macrophage Polarization. Annu Rev Physiol. 2017;79:541–566.
   PubMed Web of Science ®Google Scholar
• Hoeksema MA, Glass CK. Nature and nurture of tissue-specific macrophage phenotypes. Atherosclerosis. 2019 Feb;281:159–167.
   PubMed Web of Science ®Google Scholar
• Das A, Sinha M, Datta S, et al. Monocyte and macrophage plasticity in tissue repair and regeneration. Am J Pathol. 2015 Oct;185(10):2596–2606.
   PubMed Web of Science ®Google Scholar
• Daemen S, Schilling JD. The interplay between tissue niche and macrophage cellular metabolism in obesity. Front Immunol. 2020 Jan 22;10. DOI:10.3389/fimmu.2019.03133.
   PubMed Web of Science ®Google Scholar
• Goerdt S, Politz O, Schledzewski K, et al. Alternative versus classical activation of macrophages. Pathobiology. 1999;67(5–6):222–226.
   PubMed Web of Science ®Google Scholar
• Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 2014;6:13.
   PubMedGoogle Scholar
• Murray PJ, Allen JE, Biswas SK, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014 Jul 17;41(1):14–20.
   PubMed Web of Science ®Google Scholar
• Guilliams M, van de Laar L, Hitchhiker’s A. Guide to myeloid cell subsets: practical implementation of a novel mononuclear phagocyte classification system. Front Immunol. 2015;6:406.
   PubMed Web of Science ®Google Scholar
• Zhou JW, Tang ZW, Gao SY, et al. Tumor-associated macrophages: recent insights and therapies. Front Oncol. 2020 Feb 25;10.
   Web of Science ®Google Scholar
• Boutens L, Stienstra R. Adipose tissue macrophages: going off track during obesity. Diabetologia. 2016 May;59(5):879–894.
   PubMed Web of Science ®Google Scholar
• Takei Y, Arteel GE, Bergheim I, et al. Roles of Kupffer cells in alcoholic liver disease. Alcohol Clin Exp Res. 2005 Jun;29(6):1116–1120.
   Web of Science ®Google Scholar
• Thorbecke GJ, Silberberg-Sinakin I, Flotte TJ. Langerhans cells as macrophages in skin and lymphoid organs. J Invest Dermatol. 1980 Jul;75(1):32–43.
   PubMed Web of Science ®Google Scholar
• Li Q, Barres BA. Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol. 2018 Apr;18(4):225–242.
   PubMed Web of Science ®Google Scholar
• Ganta VC, Choi M, Farber CR, et al. Antiangiogenic VEGF(165)b regulates macrophage polarization via S100A8/S100A9 in peripheral artery disease. Circulation. 2019 Jan 8;139(2):226–242.
   PubMed Web of Science ®Google Scholar
• Okabe Y, Medzhitov R. Tissue-specific signals control reversible program of localization and functional polarization of macrophages. Cell. 2014 May 8;157(4):832–844.
   PubMed Web of Science ®Google Scholar
• Guilliams M, Mildner A, Yona S. Developmental and functional heterogeneity of monocytes. Immunity. 2018 Oct 16;49(4):595–613.
   PubMed Web of Science ®Google Scholar
• Hamers AAJ, Dinh HQ, Thomas GD, et al. Human monocyte heterogeneity as revealed by high-dimensional mass cytometry. Arteriosclerosis Thrombosis Vasc Biol. 2019 Jan;39(1):25–36.
   PubMed Web of Science ®Google Scholar
• Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005 Dec;5(12):953–964.
   PubMed Web of Science ®Google Scholar
• Ong SM, Teng KR, Newell E, et al. A novel, five-marker alternative to CD16-CD14 gating to identify the three human monocyte subsets. Front Immunol. 2019 Jul 26;10. DOI:10.3389/fimmu.2019.01761.
   Web of Science ®Google Scholar
• Shantsila E, Tapp LD, Wrigley BJ, et al. Monocyte subsets in coronary artery disease and their associations with markers of inflammation and fibrinolysis. Atherosclerosis. 2014 May;234(1):4–10.
   PubMed Web of Science ®Google Scholar
• Wildgruber M, Aschenbrenner T, Wendorff H, et al. The “Intermediate” CD14(++)CD16(+) monocyte subset increases in severe peripheral artery disease in humans. Sci Rep-Uk. 2016 Dec;19;6. DOI:10.1016/0006-2952(75)90412-8.
   Web of Science ®Google Scholar
• Hopfner F, Jacob M, Ulrich C, et al. Subgroups of monocytes predict cardiovascular events in patients with coronary heart disease. The PHAMOS trial (Prospective Halle Monocytes Study). Hellenic J Cardiol. 2019 Sep-Oct;60(5):311–321.
   PubMed Web of Science ®Google Scholar
• Berg KE, Ljungcrantz I, Andersson L, et al. Elevated CD14(++)CD16(-) monocytes predict cardiovascular events. Circulation-Cardiovasc Genet. 2012 Feb;5(1):122–131.
   PubMedGoogle Scholar
• Chaitanya GV, Cromer WE, Parker CP, et al. A recombinant inhibitory isoform of vascular endothelial growth factor(164/165) aggravates ischemic brain damage in a mouse model of focal cerebral ischemia. Am J Pathol. 2013 Sep;183(3):1010–1024.
   PubMed Web of Science ®Google Scholar
• Manetti M, Guiducci S, Ibba-Manneschi L, et al. Impaired angiogenesis in systemic sclerosis: the emerging role of the antiangiogenic VEGF(165)b splice variant. Trends Cardiovasc Med. 2011 Oct;21(7):204–210.
   PubMed Web of Science ®Google Scholar
• Konopatskaya O, Churchill A, Harper S, et al. VEGF(165)b, an endogenous C-terminal splice variant of VEGF, inhibits retinal neovascularization in mice. Mol Vis. 2006 May 26;12(67–69):626–632.
   PubMed Web of Science ®Google Scholar
• Hirigoyen D, Burgos PI, Mezzano V, et al. Inhibition of angiogenesis by platelets in systemic sclerosis patients. Arthritis Res Ther. 2015 Nov 19;17. DOI:10.1186/s13075-015-0848-2.
   PubMed Web of Science ®Google Scholar
• Gurbel PA, Fox KAA, Tantry US, et al. Combination antiplatelet and oral anticoagulant therapy in patients with coronary and peripheral artery disease focus on the COMPASS trial. Circulation. 2019 Apr 30;139(18):2170–2185.
   PubMed Web of Science ®Google Scholar
• Lee WH, Chu CY, Hsu PC, et al. Comparison of antiplatelet and antithrombotic therapy for secondary prevention of ischemic stroke in patients with peripheral artery disease - population-based follow-up study in Taiwan. Circ J. 2013 Apr;77(4):1046–1052.
   PubMed Web of Science ®Google Scholar
• Melfi R, Ricottini E. Antiplatelet therapy for peripheral artery disease. Cardiovasc Diagn Ther. 2018 Oct;8(5):663–677.
   PubMed Web of Science ®Google Scholar
• Ambati BK, Nozaki M, Singh N, et al. Corneal avascularity is due to soluble VEGF receptor-1. Nature. 2006 Oct 26;443(7114):993–997.
   PubMed Web of Science ®Google Scholar
• Ebos JML, Bocci G, Man S, et al. A naturally occurring soluble form of vascular endothelial growth factor receptor 2 detected in mouse and human plasma. Mol Cancer Res. 2004 Jun;2(6):315–326.
   PubMed Web of Science ®Google Scholar
• Mouawad R, Spano JP, Comperat E, et al. Tumoural expression and circulating level of VEGFR-3 (Flt-4) in metastatic melanoma patients: correlation with clinical parameters and outcome. Eur J Cancer. 2009 May;45(8):1407–1414.
   PubMed Web of Science ®Google Scholar
• Gagnon ML, Bielenberg DR, Gechtman Z, et al. Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: in vivo expression and antitumor activity. Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2573–2578.
   PubMed Web of Science ®Google Scholar
• Parker MW, Linkugel AD, Goel HL, et al. Structural basis for VEGF-C binding to neuropilin-2 and sequestration by a soluble splice form. Structure. 2015 Apr 7;23(4):677–687.
   PubMed Web of Science ®Google Scholar
• Hazarika S, Dokun AO, Li Y, et al. Impaired angiogenesis after Hindlimb ischemia in type 2 diabetes Mellitus - Differential regulation of vascular endothelial growth factor receptor 1 and soluble vascular endothelial growth factor receptor 1. Circ Res. 2007 Oct 26;101(9):948–956.
   PubMed Web of Science ®Google Scholar
• Wieczor R, Gadomska G, Ruszkowska-Ciastek B, et al. Impact of type 2 diabetes on the plasma levels of vascular endothelial growth factor and its soluble receptors type 1 and type 2 in patients with peripheral arterial disease. J Zhejiang Univ-Sc B. 2015 Nov;16(11):948–956.
   PubMed Web of Science ®Google Scholar
• Orecchia A, Lacal PM, Schietroma C, et al. Vascular endothelial growth factor receptor-1 is deposited in the extracellular matrix by endothelial cells and is a ligand for the alpha 5 beta 1 integrin. J Cell Sci. 2003 Sep 1;116(17):3479–3489.
   PubMed Web of Science ®Google Scholar
• Tripathi R, Ralhan R, Saxena S, et al. Soluble VEGFR-1 in pathophysiology of pregnancies complicated by hypertensive disorders: the Indian scenario. J Hum Hypertens. 2013 Feb;27(2):107–114.
   PubMed Web of Science ®Google Scholar
• Hornig C, Barleon B, Ahmad S, et al. Release and complex formation of soluble VEGFR-1 from endothelial cells and biological fluids. Lab Invest. 2000 Apr;80(4):443–454.
   PubMed Web of Science ®Google Scholar
• Kendall RL, Thomas KA. Inhibition of vascular endothelial-cell growth-factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10705–10709.
   PubMed Web of Science ®Google Scholar
• Nowak DG, Woolard J, Amin EM, et al. Expression of pro- and anti-angiogenic isoforms of VEGF is differentially regulated by splicing and growth factors. J Cell Sci. 2008 Oct 15;121(20):3487–3495.
   PubMed Web of Science ®Google Scholar
• Batson J, Toop HD, Redondo C, et al. Development of potent, selective SRPK1 inhibitors as potential topical therapeutics for neovascular eye disease. ACS Chem Biol. 2017 Mar;12(3):825–832.
   PubMed Web of Science ®Google Scholar
• Amin EM, Oltean S, Hua J, et al. WT1 mutants reveal SRPK1 to be a downstream angiogenesis target by altering VEGF splicing. Cancer Cell. 2011 Dec 13;20(6):768–780.
   PubMed Web of Science ®Google Scholar
• Yoon C, Kim D, Kim S, et al. MiR-9 regulates the post-transcriptional level of VEGF165a by targeting SRPK-1 in ARPE-19 cells. Graefes Arch Clin Exp Ophthalmol. 2014 Sep;252(9):1369–1376.
   PubMed Web of Science ®Google Scholar
• Meadows KL, Hurwitz HI. Anti-VEGF therapies in the clinic. Cold Spring Harb Perspect Med. 2012 Oct;2(10). DOI:10.1101/cshperspect.a006577.
   PubMed Web of Science ®Google Scholar
• Desideri LF, Traverso CE, Nicolo M. Abicipar pegol: an investigational anti-VEGF agent for the treatment of wet age-related macular degeneration. Expert Opin Investig Drugs. 2020 Jul 2;29(7):651–658.
   PubMed Web of Science ®Google Scholar
• Barakat MR, Kaiser PK. VEGF inhibitors for the treatment of neovascular age-related macular degeneration. Expert Opin Investig Drugs. 2009 May;18(5):637–646.
   PubMed Web of Science ®Google Scholar
• Kolls BJ, Sapp S, Rockhold FW, et al. Stroke in patients with peripheral artery disease. Stroke. 2019 Jun;50(6):1356–1363.
   PubMed Web of Science ®Google Scholar
• Olivier CB, Mulder H, Hiatt WR, et al. Incidence, characteristics, and outcomes of myocardial infarction in patients with peripheral artery disease: insights from the EUCLID trial. JAMA Cardiol. 2019 Jan 1;4(1):7–15.
   PubMed Web of Science ®Google Scholar
• Locati M, Curtale G, Mantovani A. Diversity, mechanisms, and significance of macrophage plasticity. Annu Rev Pathol. 2020;15:123–147. Vol 15, 2020.
   PubMed Web of Science ®Google Scholar