Emerging Roles for Neuropilin-2 in Cardiovascular Disease
Abstract
:1. Introduction
2. Endothelial Cell Dysfunction
2.1. Endothelial to Mesenchymal Transition
2.2. Lymphangiogenesis and Neovascularisation
3. Monocyte Recruitment and Macrophage Activity
3.1. Monocyte Recruitment
3.2. Macrophage Activity
4. VSMC Phenotypic Switching
4.1. NRPs are Expressed by Cardiovascular Precursor Cells
4.2. Nrp2 is Re-Expressed in Mature VSMCs in Response to Injury/Inflammation
5. NRP2 is an Attractive Therapeutic Target
6. Conclusions and Future Perspectives
Author Contributions
Funding
Conflicts of Interest
References
- Organization, W.H. The top 10 causes of death. 2018. Available online: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death (accessed on 1 June 2020).
- Libby, P.; Buring, J.E.; Badimon, L.; Hansson, G.K.; Deanfield, J.; Bittencourt, M.S.; Tokgozoglu, L.; Lewis, E.F. Atherosclerosis. Nat. Rev. Dis. Primers 2019, 5, 56. [Google Scholar] [CrossRef]
- McGill, H.C.; McMahan, C.A.; Herderick, E.E.; Malcom, G.T.; Tracy, R.E.; Strong, J.P. Origin of atherosclerosis in childhood and adolescence. Am. J. Clin. Nutr. 2000, 72, 1307S–1315S. [Google Scholar]
- Basatemur, G.L.; Jorgensen, H.F.; Clarke, M.C.H.; Bennett, M.R.; Mallat, Z. Vascular smooth muscle cells in atherosclerosis. Nat. Rev. Cardiol. 2019, 16, 727–744. [Google Scholar] [CrossRef] [PubMed]
- Csányi, G.; Singla, B. Arterial Lymphatics in Atherosclerosis: Old Questions, New Insights, and Remaining Challenges. J. Clin. Med. 2019, 8, 495. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tapia-Vieyra, J.V.; Delgado-Coello, B.; Mas-Oliva, J. Atherosclerosis and Cancer; A Resemblance with Far-reaching Implications. Arch. Med. Res. 2017, 48, 12–26. [Google Scholar] [CrossRef] [PubMed]
- Libby, P.; Ridker, P.M.; Hansson, G.K. Progress and challenges in translating the biology of atherosclerosis. Nature 2011, 473, 317–325. [Google Scholar] [CrossRef] [PubMed]
- Libby, P. Inflammation in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2012, 32, 2045–2051. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cuneo, A.A.; Autieri, M.V. Expression and function of anti-inflammatory interleukins: The other side of the vascular response to injury. Curr. Vasc. Pharmacol. 2009, 7, 267–276. [Google Scholar] [CrossRef] [Green Version]
- Shankman, L.S.; Gomez, D.; Cherepanova, O.A.; Salmon, M.; Alencar, G.F.; Haskins, R.M.; Swiatlowska, P.; Newman, A.A.; Greene, E.S.; Straub, A.C.; et al. KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. Nat. Med. 2015, 21, 628–637. [Google Scholar] [CrossRef] [Green Version]
- Lin, J.-D.; Nishi, H.; Poles, J.; Niu, X.; McCauley, C.; Rahman, K.; Brown, E.J.; Yeung, S.T.; Vozhilla, N.; Weinstock, A.; et al. Single-cell analysis of fate-mapped macrophages reveals heterogeneity, including stem-like properties, during atherosclerosis progression and regression. JCI Insight 2019, 4, e124574. [Google Scholar] [CrossRef] [Green Version]
- Cochain, C.; Vafadarnejad, E.; Arampatzi, P.; Pelisek, J.; Winkels, H.; Ley, K.; Wolf, D.; Saliba, A.E.; Zernecke, A. Single-Cell RNA-Seq Reveals the Transcriptional Landscape and Heterogeneity of Aortic Macrophages in Murine Atherosclerosis. Circ. Res. 2018, 122, 1661–1674. [Google Scholar] [CrossRef]
- Feil, S.; Fehrenbacher, B.; Lukowski, R.; Essmann, F.; Schulze-Osthoff, K.; Schaller, M.; Feil, R. Transdifferentiation of vascular smooth muscle cells to macrophage-like cells during atherogenesis. Circ. Res. 2014, 115, 662–667. [Google Scholar] [CrossRef] [PubMed]
- Rong, J.X.; Shapiro, M.; Trogan, E.; Fisher, E.A. Transdifferentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading. Proc. Natl. Acad. Sci. USA 2003, 100, 13531–13536. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chappell, J.; Harman, J.L.; Narasimhan, V.M.; Yu, H.; Foote, K.; Simons, B.D.; Bennett, M.R.; Jorgensen, H.F. Extensive Proliferation of a Subset of Differentiated, yet Plastic, Medial Vascular Smooth Muscle Cells Contributes to Neointimal Formation in Mouse Injury and Atherosclerosis Models. Circ. Res. 2016, 119, 1313–1323. [Google Scholar] [CrossRef] [PubMed]
- Dobnikar, L.; Taylor, A.L.; Chappell, J.; Oldach, P.; Harman, J.L.; Oerton, E.; Dzierzak, E.; Bennett, M.R.; Spivakov, M.; Jorgensen, H.F. Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels. Nat. Commun. 2018, 9, 4567. [Google Scholar] [CrossRef] [Green Version]
- Souilhol, C.; Harmsen, M.C.; Evans, P.C.; Krenning, G. Endothelial-mesenchymal transition in atherosclerosis. Cardiovasc. Res. 2018, 114, 565–577. [Google Scholar] [CrossRef] [PubMed]
- Harman, J.L.; Jorgensen, H.F. The role of smooth muscle cells in plaque stability: Therapeutic targeting potential. Br. J. Pharmacol. 2019, 176, 3741–3753. [Google Scholar] [CrossRef] [PubMed]
- Chen, P.Y.; Schwartz, M.A.; Simons, M. Endothelial-to-Mesenchymal Transition, Vascular Inflammation, and Atherosclerosis. Front. Cardiovasc. Med. 2020, 7, 53. [Google Scholar] [CrossRef]
- Helmke, A.; Casper, J.; Nordlohne, J.; David, S.; Haller, H.; Zeisberg, E.M.; von Vietinghoff, S. Endothelial-to-mesenchymal transition shapes the atherosclerotic plaque and modulates macrophage function. FASEB J. 2019, 33, 2278–2289. [Google Scholar] [CrossRef] [Green Version]
- Lai, B.; Li, Z.; He, M.; Wang, Y.; Chen, L.; Zhang, J.; Yang, Y.; Shyy, J.Y. Atheroprone flow enhances the endothelial-to-mesenchymal transition. Am. J. Physiol. Heart Circ. Physiol. 2018, 315, H1293–H1303. [Google Scholar] [CrossRef] [Green Version]
- Chen, P.Y.; Qin, L.; Li, G.; Wang, Z.; Dahlman, J.E.; Malagon-Lopez, J.; Gujja, S.; Cilfone, N.A.; Kauffman, K.J.; Sun, L.; et al. Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis. Nat. Metab. 2019, 1, 912–926. [Google Scholar] [CrossRef]
- Kofler, N.; Simons, M. The expanding role of neuropilin: Regulation of transforming growth factor-β and platelet-derived growth factor signaling in the vasculature. Curr. Opin. Hematol. 2016, 23, 260–267. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Roy, S.; Bag, A.K.; Singh, R.K.; Talmadge, J.E.; Batra, S.K.; Datta, K. Multifaceted Role of Neuropilins in the Immune System: Potential Targets for Immunotherapy. Front. Immunol. 2017, 8, 1228. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pellet-Many, C.; Frankel, P.; Jia, H.; Zachary, I. Neuropilins: Structure, function and role in disease. Biochem. J. 2008, 411, 211–226. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Issitt, T.; Bosseboeuf, E.; De Winter, N.; Dufton, N.; Gestri, G.; Senatore, V.; Chikh, A.; Randi, A.M.; Raimondi, C. Neuropilin-1 Controls Endothelial Homeostasis by Regulating Mitochondrial Function and Iron-Dependent Oxidative Stress. iScience 2019, 11, 205–223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Werneburg, S.; Buettner, F.F.; Erben, L.; Mathews, M.; Neumann, H.; Muhlenhoff, M.; Hildebrandt, H. Polysialylation and lipopolysaccharide-induced shedding of E-selectin ligand-1 and neuropilin-2 by microglia and THP-1 macrophages. Glia 2016, 64, 1314–1330. [Google Scholar] [CrossRef] [PubMed]
- Mehta, V.; Fields, L.; Evans, I.M.; Yamaji, M.; Pellet-Many, C.; Jones, T.; Mahmoud, M.; Zachary, I. VEGF (Vascular Endothelial Growth Factor) Induces NRP1 (Neuropilin-1) Cleavage via ADAMs (a Disintegrin and Metalloproteinase) 9 and 10 to Generate Novel Carboxy-Terminal NRP1 Fragments That Regulate Angiogenic Signaling. Arterioscler. Thromb. Vasc. Biol. 2018, 38, 1845–1858. [Google Scholar] [CrossRef] [Green Version]
- Schwarz, Q.; Ruhrberg, C. Neuropilin, you gotta let me know: Should I stay or should I go? Cell Adh. Migr. 2010, 4, 61–66. [Google Scholar] [CrossRef] [Green Version]
- Kitsukawa, T.; Shimizu, M.; Sanbo, M.; Hirata, T.; Taniguchi, M.; Bekku, Y.; Yagi, T.; Fujisawa, H. Neuropilin-semaphorin III/D-mediated chemorepulsive signals play a crucial role in peripheral nerve projection in mice. Neuron 1997, 19, 995–1005. [Google Scholar] [CrossRef] [Green Version]
- Soker, S.; Takashima, S.; Miao, H.Q.; Neufeld, G.; Klagsbrun, M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 1998, 92, 735–745. [Google Scholar] [CrossRef] [Green Version]
- Kawasaki, T.; Kitsukawa, T.; Bekku, Y.; Matsuda, Y.; Sanbo, M.; Yagi, T.; Fujisawa, H. A requirement for neuropilin-1 in embryonic vessel formation. Development 1999, 126, 4895–4902. [Google Scholar] [PubMed]
- Rizzolio, S.; Rabinowicz, N.; Rainero, E.; Lanzetti, L.; Serini, G.; Norman, J.; Neufeld, G.; Tamagnone, L. Neuropilin-1-dependent regulation of EGF-receptor signaling. Cancer Res. 2012, 72, 5801–5811. [Google Scholar] [CrossRef] [Green Version]
- West, D.C.; Rees, C.G.; Duchesne, L.; Patey, S.J.; Terry, C.J.; Turnbull, J.E.; Delehedde, M.; Heegaard, C.W.; Allain, F.; Vanpouille, C.; et al. Interactions of multiple heparin binding growth factors with neuropilin-1 and potentiation of the activity of fibroblast growth factor-2. J. Biol. Chem. 2005, 280, 13457–13464. [Google Scholar] [CrossRef] [Green Version]
- Hu, B.; Guo, P.; Bar-Joseph, I.; Imanishi, Y.; Jarzynka, M.J.; Bogler, O.; Mikkelsen, T.; Hirose, T.; Nishikawa, R.; Cheng, S.Y. Neuropilin-1 promotes human glioma progression through potentiating the activity of the HGF/SF autocrine pathway. Oncogene 2007, 26, 5577–5586. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jia, T.; Choi, J.; Ciccione, J.; Henry, M.; Mehdi, A.; Martinez, J.; Eymin, B.; Subra, G.; Coll, J.L. Heteromultivalent Targeting of Integrin α v β 3 and Neuropilin 1 Promotes Cell Survival via the Activation of the IGF-1/insulin Receptors. Biomaterials 2018, 155, 64–79. [Google Scholar] [CrossRef]
- Muhl, L.; Folestad, E.B.; Gladh, H.; Wang, Y.; Moessinger, C.; Jakobsson, L.; Eriksson, U. Neuropilin 1 binds PDGF-D and is a co-receptor in PDGF-D-PDGFRβ signaling. J. Cell Sci. 2017, 130, 1365–1378. [Google Scholar] [CrossRef] [Green Version]
- Pellet-Many, C.; Mehta, V.; Fields, L.; Mahmoud, M.; Lowe, V.; Evans, I.; Ruivo, J.; Zachary, I. Neuropilins 1 and 2 mediate neointimal hyperplasia and re-endothelialization following arterial injury. Cardiovasc. Res. 2015, 108, 288–298. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Grandclement, C.; Pallandre, J.R.; Valmary Degano, S.; Viel, E.; Bouard, A.; Balland, J.; Remy-Martin, J.P.; Simon, B.; Rouleau, A.; Boireau, W.; et al. Neuropilin-2 expression promotes TGF-beta1-mediated epithelial to mesenchymal transition in colorectal cancer cells. PLoS ONE 2011, 6, e20444. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mahmoud, M.; Evans, I.M.; Mehta, V.; Pellet-Many, C.; Paliashvili, K.; Zachary, I. Smooth muscle cell-specific knockout of neuropilin-1 impairs postnatal lung development and pathological vascular smooth muscle cell accumulation. Am. J. Physiol. Cell Physiol. 2019, 316, C424–C433. [Google Scholar] [CrossRef]
- Xie, X.; Urabe, G.; Marcho, L.; Williams, C.; Guo, L.W.; Kent, K.C. Smad3 Regulates Neuropilin 2 Transcription by Binding to its 5′ Untranslated Region. J. Am. Heart Assoc. 2020, 9, e015487. [Google Scholar] [CrossRef] [PubMed]
- Alsaigh, T.; Evans, D.; Frankel, D.; Torkamani, A. Decoding the transcriptome of atherosclerotic plaque at single-cell resolution. bioRxiv 2020. [Google Scholar] [CrossRef]
- Bielenberg, D.R.; Seth, A.; Shimizu, A.; Pelton, K.; Cristofaro, V.; Ramachandran, A.; Zwaans, B.M.; Chen, C.; Krishnan, R.; Seth, M.; et al. Increased smooth muscle contractility in mice deficient for neuropilin 2. Am. J. Pathol. 2012, 181, 548–559. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pellet-Many, C.; Frankel, P.; Evans, I.M.; Herzog, B.; Junemann-Ramirez, M.; Zachary, I.C. Neuropilin-1 mediates PDGF stimulation of vascular smooth muscle cell migration and signalling via p130Cas. Biochem. J. 2011, 435, 609–618. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Banerjee, S.; Sengupta, K.; Dhar, K.; Mehta, S.; D’Amore, P.A.; Dhar, G.; Banerjee, S.K. Breast cancer cells secreted platelet-derived growth factor-induced motility of vascular smooth muscle cells is mediated through neuropilin-1. Mol. Carcinog. 2006, 45, 871–880. [Google Scholar] [CrossRef] [PubMed]
- Peng, K.; Bai, Y.; Zhu, Q.; Hu, B.; Xu, Y. Targeting VEGF-neuropilin interactions: A promising antitumor strategy. Drug Discov. Today 2019, 24, 656–664. [Google Scholar] [CrossRef] [PubMed]
- Rossignol, M.; Gagnon, M.L.; Klagsbrun, M. Genomic organization of human neuropilin-1 and neuropilin-2 genes: Identification and distribution of splice variants and soluble isoforms. Genomics 2000, 70, 211–222. [Google Scholar] [CrossRef]
- Giger, R.J.; Urquhart, E.R.; Gillespie, S.K.; Levengood, D.V.; Ginty, D.D.; Kolodkin, A.L. Neuropilin-2 is a receptor for semaphorin IV: Insight into the structural basis of receptor function and specificity. Neuron 1998, 21, 1079–1092. [Google Scholar] [CrossRef] [Green Version]
- Karpanen, T.; Heckman, C.A.; Keskitalo, S.; Jeltsch, M.; Ollila, H.; Neufeld, G.; Tamagnone, L.; Alitalo, K. Functional interaction of VEGF-C and VEGF-D with neuropilin receptors. FASEB J. 2006, 20, 1462–1472. [Google Scholar] [CrossRef] [Green Version]
- Nakamura, F.; Tanaka, M.; Takahashi, T.; Kalb, R.G.; Strittmatter, S.M. Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse. Neuron 1998, 21, 1093–1100. [Google Scholar] [CrossRef] [Green Version]
- Yelland, T.; Djordjevic, S. Crystal Structure of the Neuropilin-1 MAM Domain: Completing the Neuropilin-1 Ectodomain Picture. Structure 2016, 24, 2008–2015. [Google Scholar] [CrossRef] [Green Version]
- Cai, H.; Reed, R.R. Cloning and characterization of neuropilin-1-interacting protein: A PSD-95/Dlg/ZO-1 domain-containing protein that interacts with the cytoplasmic domain of neuropilin-1. J. Neurosci. 1999, 19, 6519–6527. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, H.J.; Zheng, J.J. PDZ domains and their binding partners: Structure, specificity, and modification. Cell Commun. Signal. 2010, 8, 8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, L.; Mukhopadhyay, D.; Xu, X. C terminus of RGS-GAIP-interacting protein conveys neuropilin-1-mediated signaling during angiogenesis. FASEB J. 2006, 20, 1513–1515. [Google Scholar] [CrossRef] [PubMed]
- Tsai, Y.-C.I.; Fotinou, C.; Rana, R.; Yelland, T.; Frankel, P.; Zachary, I.; Djordjevic, S. Structural studies of neuropilin-2 reveal a zinc ion binding site remote from the vascular endothelial growth factor binding pocket. FEBS J. 2016, 283, 1921–1934. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fuh, G.; Garcia, K.C.; de Vos, A.M. The interaction of neuropilin-1 with vascular endothelial growth factor and its receptor flt-1. J. Biol. Chem. 2000, 275, 26690–26695. [Google Scholar] [CrossRef] [PubMed]
- Pan, Q.; Chanthery, Y.; Liang, W.C.; Stawicki, S.; Mak, J.; Rathore, N.; Tong, R.K.; Kowalski, J.; Yee, S.F.; Pacheco, G.; et al. Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell 2007, 11, 53–67. [Google Scholar] [CrossRef] [Green Version]
- Kawamura, H.; Li, X.; Goishi, K.; van Meeteren, L.A.; Jakobsson, L.; Cébe-Suarez, S.; Shimizu, A.; Edholm, D.; Ballmer-Hofer, K.; Kjellén, L.; et al. Neuropilin-1 in regulation of VEGF-induced activation of p38MAPK and endothelial cell organization. Blood 2008, 112, 3638–3649. [Google Scholar] [CrossRef] [Green Version]
- Caunt, M.; Mak, J.; Liang, W.C.; Stawicki, S.; Pan, Q.; Tong, R.K.; Kowalski, J.; Ho, C.; Reslan, H.B.; Ross, J.; et al. Blocking neuropilin-2 function inhibits tumor cell metastasis. Cancer Cell 2008, 13, 331–342. [Google Scholar] [CrossRef] [Green Version]
- Roth, L. The good, the bad and the ugly: A neuropilin-2 story from normal to tumor-associated lymphangiogenesis. Cell Adh. Migr. 2008, 2, 217–219. [Google Scholar] [CrossRef] [Green Version]
- Yuan, L.; Moyon, D.; Pardanaud, L.; Breant, C.; Karkkainen, M.J.; Alitalo, K.; Eichmann, A. Abnormal lymphatic vessel development in neuropilin 2 mutant mice. Development 2002, 129, 4797–4806. [Google Scholar]
- Lin, F.J.; Chen, X.; Qin, J.; Hong, Y.K.; Tsai, M.J.; Tsai, S.Y. Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel development. J. Clin. Investig. 2010, 120, 1694–1707. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takashima, S.; Kitakaze, M.; Asakura, M.; Asanuma, H.; Sanada, S.; Tashiro, F.; Niwa, H.; Miyazaki Ji, J.; Hirota, S.; Kitamura, Y.; et al. Targeting of both mouse neuropilin-1 and neuropilin-2 genes severely impairs developmental yolk sac and embryonic angiogenesis. Proc. Natl. Acad. Sci. USA 2002, 99, 3657–3662. [Google Scholar] [CrossRef] [Green Version]
- Liu, W.; Parikh, A.A.; Stoeltzing, O.; Fan, F.; McCarty, M.F.; Wey, J.; Hicklin, D.J.; Ellis, L.M. Upregulation of neuropilin-1 by basic fibroblast growth factor enhances vascular smooth muscle cell migration in response to VEGF. Cytokine 2005, 32, 206–212. [Google Scholar] [CrossRef]
- Lindner, V.; Lappi, D.A.; Baird, A.; Majack, R.A.; Reidy, M.A. Role of basic fibroblast growth factor in vascular lesion formation. Circ. Res. 1991, 68, 106–113. [Google Scholar] [CrossRef] [Green Version]
- Alexander, M.R.; Murgai, M.; Moehle, C.W.; Owens, G.K. Interleukin-1β modulates smooth muscle cell phenotype to a distinct inflammatory state relative to PDGF-DD via NF-κB-dependent mechanisms. Physiol. Genom. 2012, 44, 417–429. [Google Scholar] [CrossRef] [Green Version]
- Gruber, H.E.; Hoelscher, G.L.; Bethea, S.; Hanley, E.N., Jr. Interleukin 1-beta upregulates brain-derived neurotrophic factor, neurotrophin 3 and neuropilin 2 gene expression and NGF production in annulus cells. Biotech. Histochem. 2012, 87, 506–511. [Google Scholar] [CrossRef] [PubMed]
- Chevillard, G.; Derjuga, A.; Devost, D.; Zingg, H.H.; Blank, V. Identification of interleukin-1beta regulated genes in uterine smooth muscle cells. Reproduction 2007, 134, 811–822. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Koeck, I.; Hashemi Gheinani, A.; Baumgartner, U.; Vassella, E.; Bruggmann, R.; Burkhard, F.C.; Monastyrskaya, K. Tumor Necrosis Factor-alpha Initiates miRNA-mRNA Signaling Cascades in Obstruction-Induced Bladder Dysfunction. Am. J. Pathol. 2018, 188, 1847–1864. [Google Scholar] [CrossRef]
- Bielenberg, D.R.; Doyle, C.; Vasquez, E.; Pelton, K.; Cristofaro, V.; Sullivan, M.P.; Adam, R.M. Altered Gut Motility in Mice Lacking Neuropilin 2 in Smooth Muscle. FASEB J. 2019, 33, 496.31. [Google Scholar]
- Zachary, I. Neuropilins: Role in signalling, angiogenesis and disease. Chem. Immunol. Allergy 2014, 99, 37–70. [Google Scholar] [PubMed] [Green Version]
- Becker, P.M.; Waltenberger, J.; Yachechko, R.; Mirzapoiazova, T.; Sham, J.S.; Lee, C.G.; Elias, J.A.; Verin, A.D. Neuropilin-1 regulates vascular endothelial growth factor-mediated endothelial permeability. Circ. Res. 2005, 96, 1257–1265. [Google Scholar] [CrossRef] [Green Version]
- Maleszewska, M.; Moonen, J.R.; Huijkman, N.; van de Sluis, B.; Krenning, G.; Harmsen, M.C. IL-1β and TGFβ2 synergistically induce endothelial to mesenchymal transition in an NFκB-dependent manner. Immunobiology 2013, 218, 443–454. [Google Scholar] [CrossRef] [Green Version]
- Suzuki, H.I.; Katsura, A.; Mihira, H.; Horie, M.; Saito, A.; Miyazono, K. Regulation of TGF-β-mediated endothelial-mesenchymal transition by microRNA-27. J. Biochem. 2017, 161, 417–420. [Google Scholar] [CrossRef] [Green Version]
- Vasquez, E.; Cristofaro, V.; Lukianov, S.; Burkhard, F.C.; Gheinani, A.H.; Monastyrskaya, K.; Bielenberg, D.R.; Sullivan, M.P.; Adam, R.M. Deletion of neuropilin 2 enhances detrusor contractility following bladder outlet obstruction. JCI Insight 2017, 2, e90617. [Google Scholar] [CrossRef] [Green Version]
- Kutkut, I.; Meens, M.J.; McKee, T.A.; Bochaton-Piallat, M.L.; Kwak, B.R. Lymphatic vessels: An emerging actor in atherosclerotic plaque development. Eur. J. Clin. Investig. 2015, 45, 100–108. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, J.; Huang, Y.; Zhang, J.; Xing, B.; Xuan, W.; Wang, H.; Huang, H.; Yang, J.; Tang, J. NRP-2 in tumor lymphangiogenesis and lymphatic metastasis. Cancer Lett. 2018, 418, 176–184. [Google Scholar] [CrossRef] [PubMed]
- Tang, X.; Sun, J.; Du, L.; Du, H.; Wang, L.; Mai, J.; Zhang, F.; Liu, P. Neuropilin-2 contributes to LPS-induced corneal inflammatory lymphangiogenesis. Exp. Eye Res. 2016, 143, 110–119. [Google Scholar] [CrossRef] [PubMed]
- Shen, J.; Samul, R.; Zimmer, J.; Liu, H.; Liang, X.; Hackett, S.; Campochiaro, P.A. Deficiency of neuropilin 2 suppresses VEGF-induced retinal neovascularization. Mol. Med. (Camb. Mass.) 2004, 10, 12–18. [Google Scholar] [CrossRef]
- Favier, B.; Alam, A.; Barron, P.; Bonnin, J.; Laboudie, P.; Fons, P.; Mandron, M.; Herault, J.P.; Neufeld, G.; Savi, P.; et al. Neuropilin-2 interacts with VEGFR-2 and VEGFR-3 and promotes human endothelial cell survival and migration. Blood 2006, 108, 1243–1250. [Google Scholar] [CrossRef]
- Xu, Y.; Yuan, L.; Mak, J.; Pardanaud, L.; Caunt, M.; Kasman, I.; Larrivée, B.; del Toro, R.; Suchting, S.; Medvinsky, A.; et al. Neuropilin-2 mediates VEGF-C-induced lymphatic sprouting together with VEGFR3. J. Cell Biol. 2010, 188, 115–130. [Google Scholar] [CrossRef] [Green Version]
- James, J.M.; Nalbandian, A.; Mukouyama, Y.-S. TGFβ signaling is required for sprouting lymphangiogenesis during lymphatic network development in the skin. Development (Cambridge, England) 2013, 140, 3903–3914. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cao, Y.; Hoeppner, L.H.; Bach, S.; Cao, Y.; Hoeppner, L.H.; Bach, S.; Guangqi, E.; Guo, Y.; Wang, E.; Wu, J.; et al. Neuropilin-2 promotes extravasation and metastasis by interacting with endothelial alpha5 integrin. Cancer Res. 2013, 73, 4579–4590. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ou, J.J.; Wei, X.; Peng, Y.; Zha, L.; Zhou, R.B.; Shi, H.; Zhou, Q.; Liang, H.J. Neuropilin-2 mediates lymphangiogenesis of colorectal carcinoma via a VEGFC/VEGFR3 independent signaling. Cancer Lett. 2015, 358, 200–209. [Google Scholar] [CrossRef] [PubMed]
- Finney, A.C.; Stokes, K.Y.; Pattillo, C.B.; Orr, A.W. Integrin signaling in atherosclerosis. Cell. Mol. Life Sci. 2017, 74, 2263–2282. [Google Scholar] [CrossRef] [PubMed]
- Sun, X.; Fu, Y.; Gu, M.; Zhang, L.; Li, D.; Li, H.; Chien, S.; Shyy, J.Y.; Zhu, Y. Activation of integrin alpha5 mediated by flow requires its translocation to membrane lipid rafts in vascular endothelial cells. Proc. Natl. Acad. Sci. USA 2016, 113, 769–774. [Google Scholar] [CrossRef] [Green Version]
- Yun, S.; Budatha, M.; Dahlman, J.E.; Coon, B.G.; Cameron, R.T.; Langer, R.; Anderson, D.G.; Baillie, G.; Schwartz, M.A. Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling. Nat. Cell Biol. 2016, 18, 1043–1053. [Google Scholar] [CrossRef]
- Yurdagul, A., Jr.; Green, J.; Albert, P.; McInnis, M.C.; Mazar, A.P.; Orr, A.W. α5β1 integrin signaling mediates oxidized low-density lipoprotein-induced inflammation and early atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2014, 34, 1362–1373. [Google Scholar] [CrossRef] [Green Version]
- Xu, X.; Mao, W.; Chai, Y.; Dai, J.; Chen, Q.; Wang, L.; Zhuang, Q.; Pan, Y.; Chen, M.; Ni, G.; et al. Angiogenesis Inhibitor, Endostar, Prevents Vasa Vasorum Neovascularization in a Swine Atherosclerosis Model. J. Atheroscler. Thromb. 2015, 22, 1100–1112. [Google Scholar] [CrossRef] [Green Version]
- Alghamdi, A.A.A.; Benwell, C.J.; Atkinson, S.J.; Lambert, J.; Johnson, R.T.; Robinson, S.D. NRP2 as an Emerging Angiogenic Player; Promoting Endothelial Cell Adhesion and Migration by Regulating Recycling of α5 Integrin. Front. Cell Dev. Biol. 2020, 8, 395. [Google Scholar] [CrossRef]
- Mumblat, Y.; Kessler, O.; Ilan, N.; Neufeld, G. Full-Length Semaphorin-3C Is an Inhibitor of Tumor Lymphangiogenesis and Metastasis. Cancer Res. 2015, 75, 2177–2186. [Google Scholar] [CrossRef] [Green Version]
- Wu, F.; Zhou, Q.; Yang, J.; Duan, G.J.; Ou, J.J.; Zhang, R.; Pan, F.; Peng, Q.P.; Tan, H.; Ping, Y.F.; et al. Endogenous axon guiding chemorepulsant semaphorin-3F inhibits the growth and metastasis of colorectal carcinoma. Clin. Cancer Res. 2011, 17, 2702–2711. [Google Scholar] [CrossRef] [Green Version]
- Toledano, S.; Nir-Zvi, I.; Engelman, R.; Kessler, O.; Neufeld, G. Class. 3 Semaphorins and Their Receptors: Potent Multifunctional Modulators of Tumor Progression. Int. J. Mol. Sci. 2019, 20, 556. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nakayama, H.; Bruneau, S.; Kochupurakkal, N.; Coma, S.; Briscoe, D.M.; Klagsbrun, M. Regulation of mTOR Signaling by Semaphorin 3F-Neuropilin 2 Interactions In Vitro and In Vivo. Sci. Rep. 2015, 5, 11789. [Google Scholar] [CrossRef] [Green Version]
- Kutschera, S.; Weber, H.; Weick, A.; De Smet, F.; Genove, G.; Takemoto, M.; Prahst, C.; Riedel, M.; Mikelis, C.; Baulande, S.; et al. Differential endothelial transcriptomics identifies semaphorin 3G as a vascular class 3 semaphorin. Arterioscler. Thromb. Vasc. Biol. 2011, 31, 151–159. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mucka, P.; Levonyak, N.; Geretti, E.; Zwaans, B.M.M.; Li, X.; Adini, I.; Klagsbrun, M.; Adam, R.M.; Bielenberg, D.R. Inflammation and Lymphedema Are Exacerbated and Prolonged by Neuropilin 2 Deficiency. Am. J. Clin. Pathol. 2016, 186, 2803–2812. [Google Scholar] [CrossRef] [Green Version]
- Guo, H.-F.; Li, X.; Parker, M.W.; Waltenberger, J.; Becker, P.M.; Vander Kooi, C.W. Mechanistic basis for the potent anti-angiogenic activity of semaphorin 3F. Biochem. 2013, 52, 7551–7558. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, X.; Uemura, A.; Fukushima, Y.; Yoshida, Y.; Hirashima, M. Semaphorin 3G Provides a Repulsive Guidance Cue to Lymphatic Endothelial Cells via Neuropilin-2/PlexinD1. Cell Rep. 2016, 17, 2299–2311. [Google Scholar] [CrossRef] [Green Version]
- Sodhi, A.; Ma, T.; Menon, D.; Deshpande, M.; Jee, K.; Dinabandhu, A.; Vancel, J.; Lu, D.; Montaner, S. Angiopoietin-like 4 binds neuropilins and cooperates with VEGF to induce diabetic macular edema. J. Clin. Investig. 2019, 129, 4593–4608. [Google Scholar] [CrossRef]
- Maguire, E.M.; Pearce, S.W.A.; Xiao, Q. Foam cell formation: A new target for fighting atherosclerosis and cardiovascular disease. Vascul. Pharmacol. 2019, 112, 54–71. [Google Scholar] [CrossRef]
- Dupuy, A.G.; Caron, E. Integrin-dependent phagocytosis: Spreading from microadhesion to new concepts. J. Cell Sci. 2008, 121, 1773–1783. [Google Scholar] [CrossRef] [Green Version]
- Chellenburg, S.; Schulz, A.; Poitz, D.M.; Muders, M.H. Role of neuropilin-2 in the immune system. Mol. Immunol. 2017, 90, 239–244. [Google Scholar] [CrossRef]
- Roy, S.; Bag, A.K.; Dutta, S.; Polavaram, N.S.; Islam, R.; Schellenburg, S.; Banwait, J.; Guda, C.; Ran, S.; Hollingsworth, M.A.; et al. Macrophage-Derived Neuropilin-2 Exhibits Novel Tumor-Promoting Functions. Cancer Res. 2018, 78, 5600–5617. [Google Scholar] [CrossRef] [Green Version]
- Aung, N.Y.; Ohe, R.; Meng, H.; Kabasawa, T.; Yang, S.; Kato, T.; Yamakawa, M. Specific Neuropilins Expression in Alveolar Macrophages among Tissue-Specific Macrophages. PloS ONE 2016, 11, e0147358. [Google Scholar] [CrossRef] [PubMed]
- Stamatos, N.M.; Zhang, L.; Jokilammi, A.; Finne, J.; Chen, W.H.; El-Maarouf, A.; Cross, A.S.; Hankey, K.G. Changes in polysialic acid expression on myeloid cells during differentiation and recruitment to sites of inflammation: Role in phagocytosis. Glycobiol. 2014, 24, 864–879. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shahraz, A.; Kopatz, J.; Mathy, R.; Kappler, J.; Winter, D.; Kapoor, S.; Schütza, V.; Scheper, T.; Gieselmann, V.; Neumann, H. Anti-inflammatory activity of low molecular weight polysialic acid on human macrophages. Sci. Rep. 2015, 5, 16800. [Google Scholar] [CrossRef] [Green Version]
- Immormino, R.M.; Lauzier, D.C.; Nakano, H.; Hernandez, M.L.; Alexis, N.E.; Ghio, A.J.; Tilley, S.L.; Doerschuk, C.M.; Peden, D.B.; Cook, D.N.; et al. Neuropilin-2 regulates airway inflammatory responses to inhaled lipopolysaccharide. Am. J. Physiol. Lung Cell Mol. Physiol. 2018, 315, L202–L211. [Google Scholar] [CrossRef] [PubMed]
- Parker, M.W.; Linkugel, A.D.; Goel, H.L.; Wu, T.; Mercurio, A.M.; Vander Kooi, C.W. Structural basis for VEGF-C binding to neuropilin-2 and sequestration by a soluble splice form. Structure 2015, 23, 677–687. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ding, S.; Ma, M.; Negro, A.; Berry, C.; Kovacic, J.C.; Cimato, T.R.; Boehm, M. Neuropilin-2 Identifies Cardiovascular Precursor Cells and is Required for Vascular Differentiation in Murine Embryonic Stem Cells System. J. Stem. Cell Res. Transpl. 2015, 2, 1017. [Google Scholar]
- Herzog, Y.; Kalcheim, C.; Kahane, N.; Reshef, R.; Neufeld, G. Differential expression of neuropilin-1 and neuropilin-2 in arteries and veins. Mech. Dev. 2001, 109, 115–119. [Google Scholar] [CrossRef]
- Wiszniak, S.; Scherer, M.; Ramshaw, H.; Schwarz, Q. Neuropilin-2 genomic elements drive cre recombinase expression in primitive blood, vascular and neuronal lineages. Genesis 2015, 53, 709–717. [Google Scholar] [CrossRef]
- Wong, A.P.; Nili, N.; Strauss, B.H. In vitro differences between venous and arterial-derived smooth muscle cells: Potential modulatory role of decorin. Cardiovasc. Res. 2005, 65, 702–710. [Google Scholar] [CrossRef] [PubMed]
- Elaimy, A.L.; Guru, S.; Chang, C.; Ou, J.; Amante, J.J.; Zhu, L.J.; Goel, H.L.; Mercurio, A.M. VEGF-neuropilin-2 signaling promotes stem-like traits in breast cancer cells by TAZ-mediated repression of the Rac GAP β2-chimaerin. Sci. Signal 2018, 11. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klagsbrun, M.; Takashima, S.; Mamluk, R. The role of neuropilin in vascular and tumor biology. Adv. Exp. Med. Biol. 2002, 515, 33–48. [Google Scholar] [PubMed]
- Alberts-Grill, N.; Rezvan, A.; Son, D.J.; Qiu, H.; Kim, C.W.; Kemp, M.L.; Weyand, C.M.; Jo, H. Dynamic immune cell accumulation during flow-induced atherogenesis in mouse carotid artery: An expanded flow cytometry method. Arterioscler. Thromb. Vasc. Biol. 2012, 32, 623–632. [Google Scholar] [CrossRef] [Green Version]
- Herring, B.P.; Hoggatt, A.M.; Griffith, S.L.; McClintick, J.N.; Gallagher, P.J. Inflammation and vascular smooth muscle cell dedifferentiation following carotid artery ligation. Physiol. Genom. 2017, 49, 115–126. [Google Scholar] [CrossRef]
- Choi, S.; Park, M.; Kim, J.; Park, W.; Kim, S.; Lee, D.K.; Hwang, J.Y.; Choe, J.; Won, M.H.; Ryoo, S.; et al. TNF-alpha elicits phenotypic and functional alterations of vascular smooth muscle cells by miR-155-5p-dependent down-regulation of cGMP-dependent kinase 1. J. Biol. Chem. 2018, 293, 14812–14822. [Google Scholar] [CrossRef] [Green Version]
- Yoshida, T.; Yamashita, M.; Horimai, C.; Hayashi, M. Smooth muscle-selective inhibition of nuclear factor-kappaB attenuates smooth muscle phenotypic switching and neointima formation following vascular injury. J. Am. Heart Assoc. 2013, 2, e000230. [Google Scholar] [CrossRef] [Green Version]
- Tang, R.H.; Zheng, X.L.; Callis, T.E.; Stansfield, W.E.; He, J.; Baldwin, A.S.; Wang, D.Z.; Selzman, C.H. Myocardin inhibits cellular proliferation by inhibiting NF-kappaB(p65)-dependent cell cycle progression. Proc. Natl. Acad. Sci. USA 2008, 105, 3362–3367. [Google Scholar] [CrossRef] [Green Version]
- Singh, P.; Zheng, X.L. Dual regulation of myocardin expression by tumor necrosis factor-alpha in vascular smooth muscle cells. Plos ONE 2014, 9, e112120. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Said, A.M.; Parker, M.W.; Vander Kooi, C.W. Design, synthesis, and evaluation of a novel benzamidine-based inhibitor of VEGF-C binding to Neuropilin-2. Bioorg. Chem. 2020, 100, 103856. [Google Scholar] [CrossRef] [PubMed]
- Nicholls, S.J.; Puri, R.; Anderson, T.; Ballantyne, C.M.; Cho, L.; Kastelein, J.J.P.; Koenig, W.; Somaratne, R.; Kassahun, H.; Yang, J.; et al. Effect of Evolocumab on Coronary Plaque Composition. J. Am. Coll. Cardiol. 2018, 72, 2012–2021. [Google Scholar] [CrossRef] [PubMed]
- Ridker, P.M. Canakinumab for Residual Inflammatory Risk. Eur. Heart J. 2017, 38, 3545–3548. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sabatine, M.S.; Leiter, L.A.; Wiviott, S.D.; Giugliano, R.P.; Deedwania, P.; De Ferrari, G.M.; Murphy, S.A.; Kuder, J.F.; Gouni-Berthold, I.; Lewis, B.S.; et al. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: A prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol. 2017, 5, 941–950. [Google Scholar] [CrossRef]
- Chen, L.; Wang, L.; Yan, J.; Ma, C.; Lu, J.; Chen, G.; Chen, S.; Su, F.; Wang, W.; Su, X. 131I-labeled monoclonal antibody targeting neuropilin receptor type-2 for tumor SPECT imaging. Int. J. Oncol. 2017, 50, 649–659. [Google Scholar] [CrossRef] [PubMed]
- Reimann, C.; Brangsch, J.; Colletini, F.; Walter, T.; Hamm, B.; Botnar, R.M.; Makowski, M.R. Molecular imaging of the extracellular matrix in the context of atherosclerosis. Adv. Drug. Deliv. Rev. 2017, 113, 49–60. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Niland, S.; Eble, J.A. Neuropilins in the Context of Tumor Vasculature. Int. J. Mol. Sci. 2019, 20, 639. [Google Scholar] [CrossRef] [Green Version]
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Harman, J.L.; Sayers, J.; Chapman, C.; Pellet-Many, C. Emerging Roles for Neuropilin-2 in Cardiovascular Disease. Int. J. Mol. Sci. 2020, 21, 5154. https://doi.org/10.3390/ijms21145154
Harman JL, Sayers J, Chapman C, Pellet-Many C. Emerging Roles for Neuropilin-2 in Cardiovascular Disease. International Journal of Molecular Sciences. 2020; 21(14):5154. https://doi.org/10.3390/ijms21145154
Chicago/Turabian StyleHarman, Jennifer L., Jacob Sayers, Chey Chapman, and Caroline Pellet-Many. 2020. "Emerging Roles for Neuropilin-2 in Cardiovascular Disease" International Journal of Molecular Sciences 21, no. 14: 5154. https://doi.org/10.3390/ijms21145154