C. Nusslein-volhard and E. Wieschaus, Mutations affecting segment number and polarity in Drosophila, Nature, vol.287, pp.795-801, 1980.

M. J. Bitgood and A. P. Mcmahon, Hedgehog and Bmp genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo, Dev. Biol, vol.172, pp.126-138, 1995.

M. Ramalho-santos, D. A. Melton, and A. P. Mcmahon, Hedgehog signals regulate multiple aspects of gastrointestinal development, Development, vol.127, pp.2763-2772, 2000.

B. St-jacques, M. Hammerschmidt, and A. P. Mcmahon, Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation, Genes Dev, vol.13, pp.2072-2086, 1999.

M. J. Bitgood, L. Shen, and A. P. Mcmahon, Sertoli cell signaling by Desert hedgehog regulates the male germline, Curr. Biol, vol.6, pp.298-304, 1996.

E. Parmantier, B. Lynn, D. Lawson, M. Turmaine, S. S. Namini et al., Schwann cell-derived Desert hedgehog controls the development of peripheral nerve sheaths, Neuron, vol.23, pp.713-724, 1999.

R. Petrova and A. L. Joyner, Roles for Hedgehog signaling in adult organ homeostasis and repair, vol.141, pp.3445-3457, 2014.

S. J. Scales and F. J. De-sauvage, Mechanisms of Hedgehog pathway activation in cancer and implications for therapy, Trends Pharm. Sci, vol.30, pp.303-312, 2009.

C. V. Pepicelli, P. M. Lewis, and A. P. Mcmahon, Sonic hedgehog regulates branching morphogenesis in the mammalian lung, Curr. Biol, vol.8, pp.1083-1086, 1998.

D. H. Rowitch, B. Jacques, S. M. Lee, J. D. Flax, E. Y. Snyder et al., Sonic hedgehog regulates proliferation and inhibits differentiation of CNS precursor cells, J. Neurosci, vol.19, pp.8954-8965, 1999.

R. Pola, L. E. Ling, M. Silver, M. J. Corbley, M. Kearney et al., The morphogen Sonic hedgehog is an indirect angiogenic agent upregulating two families of angiogenic growth factors, Nat. Med, vol.7, pp.706-711, 2001.

M. A. Renault, J. Roncalli, J. Tongers, T. Thorne, E. Klyachko et al., Sonic hedgehog induces angiogenesis via Rho kinase-dependent signaling in endothelial cells, J. Mol. Cell. Cardiol, vol.49, pp.490-498, 2010.

K. Fujita, T. Miyamoto, and S. Saika, Sonic hedgehog: Its expression in a healing cornea and its role in neovascularization, Mol. Vis, vol.15, pp.1036-1044, 2009.

Q. Yao, M. A. Renault, C. Chapouly, S. Vandierdonck, I. Belloc et al., Sonic hedgehog mediates a novel pathway of PDGF-BB-dependent vessel maturation, Blood, vol.123, pp.2429-2437, 2014.
URL : https://hal.archives-ouvertes.fr/inserm-01784115

J. I. Alvarez, A. Dodelet-devillers, H. Kebir, I. Ifergan, P. J. Fabre et al., The Hedgehog Pathway Promotes Blood-Brain Barrier Integrity and CNS Immune Quiescence, Science, vol.334, pp.1727-1731, 2011.

, Int. J. Mol. Sci, vol.20, pp.3076-3093, 2019.

N. D. Lawson, A. M. Vogel, and B. M. Weinstein, Sonic hedgehog and vascular endothelial growth factor act upstream of the Notch pathway during arterial endothelial differentiation, Dev. Cell, vol.3, pp.127-136, 2002.

K. J. Lavine and D. M. Ornitz, Rebuilding the coronary vasculature: Hedgehog as a new candidate for pharmacologic revascularization, Trends Cardiovasc. Med, vol.17, pp.77-83, 2007.

B. Cristofaro and C. Emanueli, Possible novel targets for therapeutic angiogenesis, Curr. Opin. Pharmacol, vol.9, pp.102-108, 2009.

J. Y. Pan and S. H. Zhou, The hedgehog signaling pathway, a new therapeutic target for treatment of ischemic heart disease, Pharmazie, vol.67, pp.475-481, 2012.

Y. Wang, P. Lu, D. Zhao, and J. Sheng, Targeting the hedgehog signaling pathway for cardiac repair and regeneration, vol.42, pp.662-668, 2017.

M. Dunaeva and J. Waltenberger, Hh signaling in regeneration of the ischemic heart, Cell. Mol. Life Sci, vol.74, pp.3481-3490, 2017.

A. A. Salybekov, A. K. Salybekova, R. Pola, and T. Asahara, Sonic Hedgehog Signaling Pathway in Endothelial Progenitor Cell Biology for Vascular Medicine, Int. J. Mol. Sci, vol.19, 2018.

S. F. Farzan, S. Singh, N. S. Schilling, and D. J. Robbins, Hedgehog Processing and Biological Activity, Am. J. Physiol. Gastrointest. Liver Physiol, vol.294, pp.844-849, 2008.

C. A. Pettigrew, E. Asp, and C. P. Emerson, A new role for Hedgehogs in juxtacrine signaling, Mech. Dev, vol.131, pp.137-149, 2013.

H. Tukachinsky, R. P. Kuzmickas, C. Y. Jao, J. Liu, and A. Salic, Dispatched and scube mediate the efficient secretion of the cholesterol-modified hedgehog ligand, Cell Rep, vol.2, pp.308-320, 2012.

D. J. Robbins, D. L. Fei, and N. A. Riobo, The Hedgehog signal transduction network, Sci. Signal, vol.5, p.6, 2012.

S. A. Ramsbottom and M. E. Pownall, Regulation of Hedgehog Signalling Inside and Outside the Cell, J. Dev. Biol, 2016.

F. Bangs and K. V. Anderson, Primary Cilia and Mammalian Hedgehog Signaling, Cold Spring Harb. Perspect Biol, vol.9, 2017.

N. Byrd, S. Becker, P. Maye, R. Narasimhaiah, B. St-jacques et al., Hedgehog is required for murine yolk sac angiogenesis, vol.129, pp.361-372, 2002.

M. A. Dyer, S. M. Farrington, D. Mohn, J. R. Munday, and M. H. Baron, Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify prospective neurectodermal cell fate in the mouse embryo, vol.128, pp.1717-1730, 2001.

M. Nagase, T. Nagase, I. Koshima, and T. Fujita, Critical time window of hedgehog-dependent angiogenesis in murine yolk sac, Microvasc. Res, vol.71, pp.85-90, 2006.

J. Astorga and P. Carlsson, Hedgehog induction of murine vasculogenesis is mediated by Foxf1 and Bmp4, vol.134, pp.3753-3761, 2007.

E. Hochman, A. Castiel, J. Jacob-hirsch, N. Amariglio, and S. Izraeli, Molecular pathways regulating pro-migratory effects of Hedgehog signaling, J. Biol. Chem, vol.281, pp.33860-33870, 2006.

L. D. Miller, S. E. Wert, J. C. Clark, Y. Xu, A. T. Perl et al., Role of Sonic hedgehog in patterning of tracheal-bronchial cartilage and the peripheral lung, Dev. Dyn, vol.231, pp.57-71, 2004.

A. C. White, K. J. Lavine, and D. M. Ornitz, FGF9 and SHH regulate mesenchymal Vegfa expression and development of the pulmonary capillary network, Development, vol.134, pp.3743-3752, 2007.

M. Van-tuyl, F. Groenman, J. Wang, M. Kuliszewski, J. Liu et al., Angiogenic factors stimulate tubular branching morphogenesis of sonic hedgehog-deficient lungs, Dev. Biol, vol.303, pp.514-526, 2007.

H. Seo, J. Kim, G. Park, Y. Kim, and S. Cho, Long-range enhancers modulate Foxf1 transcription in blood vessels of pulmonary vascular network, Histochem. Cell Biol, vol.146, pp.289-300, 2016.

S. A. Vokes, T. A. Yatskievych, R. L. Heimark, J. Mcmahon, A. P. Mcmahon et al., Hedgehog signaling is essential for endothelial tube formation during vasculogenesis, Development, vol.131, pp.4371-4380, 2004.

H. Kolesova, H. Roelink, and M. Grim, Sonic hedgehog is required for the assembly and remodeling of branchial arch blood vessels, Dev. Dyn, vol.237, pp.1923-1934, 2008.

, Int. J. Mol. Sci, vol.20, pp.3076-3094, 2019.

C. M. Moran, M. C. Salanga, and P. A. Krieg, Hedgehog signaling regulates size of the dorsal aortae and density of the plexus during avian vascular development, Dev. Dyn, vol.240, pp.1354-1364, 2011.

L. Coultas, E. Nieuwenhuis, G. A. Anderson, J. Cabezas, A. Nagy et al., Hedgehog regulates distinct vascular patterning events through VEGF-dependent and -independent mechanisms, Blood, vol.116, pp.653-660, 2010.

L. A. Brown, A. R. Rodaway, T. F. Schilling, T. Jowett, P. W. Ingham et al., Insights into early vasculogenesis revealed by expression of the ETS-domain transcription factor Fli-1 in wild-type and mutant zebrafish embryos, Mech. Dev, vol.90, pp.237-252, 2000.

C. Williams, S. Kim, T. T. Ni, L. Mitchell, H. Ro et al., Hedgehog signaling induces arterial endothelial cell formation by repressing venous cell fate, Dev. Biol, vol.341, pp.196-204, 2010.

T. Nagase, M. Nagase, K. Yoshimura, M. Machida, and M. Yamagishi, Defects in aortic fusion and craniofacial vasculature in the holoprosencephalic mouse embryo under inhibition of sonic hedgehog signaling, J. Craniofac. Surg, vol.17, pp.736-744, 2006.

S. Nicoli, C. Tobia, L. Gualandi, G. De-sena, and M. Presta, Calcitonin receptor-like receptor guides arterial differentiation in zebrafish, Blood, vol.111, pp.4965-4972, 2008.

R. E. Lamont, W. Vu, A. D. Carter, F. C. Serluca, C. A. Macrae et al., Hedgehog signaling via angiopoietin1 is required for developmental vascular stability, Mech. Dev, vol.127, pp.159-168, 2010.

E. M. Surace, K. S. Balaggan, A. Tessitore, C. Mussolino, G. Cotugno et al., Inhibition of ocular neovascularization by hedgehog blockade, Mol. Ther, vol.13, pp.573-579, 2006.

T. E. Walshe, P. Connell, L. Cryan, G. Ferguson, T. Gardiner et al., Microvascular retinal endothelial and pericyte cell apoptosis in vitro: Role of hedgehog and Notch signaling, Investig. Ophthalmol. Vis. Sci, vol.52, pp.4472-4483, 2011.

C. A. Berrios-otero, Y. Z. Wadghiri, B. J. Nieman, A. L. Joyner, and D. H. Turnbull, Three-dimensional micro-MRI analysis of cerebral artery development in mouse embryos, Magn. Reson. Med, vol.62, pp.1431-1439, 2009.

C. M. Nielsen and S. M. Dymecki, Sonic hedgehog is required for vascular outgrowth in the hindbrain choroid plexus, Dev. Biol, vol.340, pp.430-437, 2010.

C. Colnot, L. De-la-fuente, S. Huang, D. Hu, C. Lu et al., Indian hedgehog synchronizes skeletal angiogenesis and perichondrial maturation with cartilage development, Development, vol.132, pp.1057-1067, 2005.

E. Dohle, S. Fuchs, M. Kolbe, A. Hofmann, H. Schmidt et al., Sonic hedgehog promotes angiogenesis and osteogenesis in a coculture system consisting of primary osteoblasts and outgrowth endothelial cells, Tissue Eng. Part A, vol.16, pp.1235-1237, 2010.

X. Duan, Y. Murata, Y. Liu, C. Nicolae, B. R. Olsen et al., Vegfa regulates perichondrial vascularity and osteoblast differentiation in bone development, vol.142, 1984.

K. J. Lavine, A. C. White, C. Park, C. S. Smith, K. Choi et al., Fibroblast growth factor signals regulate a wave of Hedgehog activation that is essential for coronary vascular development, Genes Dev, vol.20, pp.1651-1666, 2006.

K. J. Lavine, F. Long, K. Choi, C. Smith, and D. M. Ornitz, Hedgehog signaling to distinct cell types differentially regulates coronary artery and vein development, Development, vol.135, pp.3161-3171, 2008.

C. M. Moran, C. T. Myers, C. M. Lewis, and P. A. Krieg, Hedgehog regulates angiogenesis of intersegmental vessels through the VEGF signaling pathway, Dev. Dyn, vol.241, pp.1034-1042, 2012.

Y. Ren, R. G. Cowan, F. F. Migone, and S. M. Quirk, Overactivation of hedgehog signaling alters development of the ovarian vasculature in mice, Biol. Reprod, vol.86, 2012.

O. Weiss, R. Kaufman, E. Mishani, and A. Inbal, Ocular vessel patterning in zebrafish is indirectly regulated by Hedgehog signaling, Int. J. Dev. Biol, vol.61, pp.277-284, 2017.

M. G. Davey, J. James, I. R. Paton, D. W. Burt, and C. Tickle, Analysis of talpid3 and wild-type chicken embryos reveals roles for Hedgehog signalling in development of the limb bud vasculature, Dev. Biol, vol.301, pp.155-165, 2007.

, Int. J. Mol. Sci, vol.20, pp.3076-3095, 2019.

W. Chen, T. Tang, J. Eastham-anderson, D. Dunlap, B. Alicke et al., Canonical hedgehog signaling augments tumor angiogenesis by induction of VEGF-A in stromal perivascular cells, Proc. Natl. Acad. Sci, vol.108, pp.9589-9594, 2011.

R. Pola, L. E. Ling, T. R. Aprahamian, E. Barban, M. Bosch-marce et al., Postnatal recapitulation of embryonic hedgehog pathway in response to skeletal muscle ischemia, Circulation, vol.108, pp.479-485, 2003.

M. A. Renault, C. Chapouly, Q. Yao, F. Larrieu-lahargue, S. Vandierdonck et al., Desert hedgehog promotes ischemia-induced angiogenesis by ensuring peripheral nerve survival, Circ. Res, vol.112, pp.762-770, 2013.
URL : https://hal.archives-ouvertes.fr/inserm-01779144

M. Palladino, I. Gatto, V. Neri, S. Straino, M. Silver et al., Pleiotropic beneficial effects of sonic hedgehog gene therapy in an experimental model of peripheral limb ischemia, Mol. Ther, vol.19, pp.658-666, 2011.

M. A. Renault, F. Robbesyn, C. Chapouly, Q. Yao, S. Vandierdonck et al., Hedgehog-dependent regulation of angiogenesis and myogenesis is impaired in aged mice, Arter. Thromb. Vasc. Biol, vol.33, pp.2858-2866, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00919989

M. A. Renault, J. Roncalli, J. Tongers, S. Misener, T. Thorne et al., The Hedgehog transcription factor Gli3 modulates angiogenesis, Circ. Res, vol.105, pp.818-826, 2009.

C. Caradu, A. Guy, C. James, A. Reynaud, A. Gadeau et al., Endogenous Sonic Hedgehog limits inflammation and angiogenesis in the ischaemic skeletal muscle of mice, Cardiovasc. Res, vol.114, pp.759-770, 2018.

T. Benameur, R. Soleti, C. Porro, R. Andriantsitohaina, and M. C. Martínez, Microparticles carrying Sonic hedgehog favor neovascularization through the activation of nitric oxide pathway in mice, PLoS ONE, vol.5, 2010.

Y. Qin, Y. He, N. Hou, G. Zhang, Y. Cai et al., Sonic hedgehog improves ischemia-induced neovascularization by enhancing endothelial progenitor cell function in type 1 diabetes, Mol. Cell. Endocrinol, vol.423, pp.30-39, 2016.

M. A. Renault, S. Vandierdonck, C. Chapouly, Y. Yu, G. Qin et al., Gli3 regulation of myogenesis is necessary for ischemia-induced angiogenesis, Circ. Res, vol.113, pp.1148-1158, 2013.
URL : https://hal.archives-ouvertes.fr/inserm-01777743

R. Gupta, A. R. Mackie, S. Misener, L. Liu, D. W. Losordo et al., Endothelial smoothened-dependent hedgehog signaling is not required for sonic hedgehog induced angiogenesis or ischemic tissue repair, Lab. Investig, vol.98, pp.682-691, 2018.

G. Straface, T. Aprahamian, A. Flex, E. Gaetani, F. Biscetti et al., Sonic hedgehog regulates angiogenesis and myogenesis during post-natal skeletal muscle regeneration, J. Cell. Mol. Med, vol.13, pp.2424-2435, 2009.

A. Piccioni, E. Gaetani, V. Neri, I. Gatto, M. Palladino et al., Sonic Hedgehog Therapy in a Mouse Model of Age-Associated Impairment of Skeletal Muscle Regeneration, J. Gerontol, vol.69, pp.245-252, 2013.

K. F. Kusano, R. Pola, T. Murayama, C. Curry, A. Kawamoto et al., Sonic hedgehog myocardial gene therapy: Tissue repair through transient reconstitution of embryonic signaling, Nat. Med, vol.11, pp.1197-1204, 2005.

R. P. Ahmed, K. H. Haider, J. Shujia, M. R. Afzal, and M. Ashraf, Sonic Hedgehog gene delivery to the rodent heart promotes angiogenesis via iNOS/netrin-1/PKC pathway, PLoS ONE, vol.5, 2010.

Y. Jin, A. Barnett, Y. Zhang, X. Yu, and Y. Luo, Poststroke Sonic Hedgehog Agonist Treatment Improves Functional Recovery by Enhancing Neurogenesis and Angiogenesis, vol.48, pp.1636-1645, 2017.

S. Chen, M. Huang, Q. He, Y. Zhang, E. N. Opoku et al., Administration of sonic hedgehog protein induces angiogenesis and has therapeutic effects after stroke in rats, vol.352, pp.285-295, 2017.

, Int. J. Mol. Sci, vol.20, p.24, 2019.

O. V. Chechneva, F. Mayrhofer, D. J. Daugherty, R. G. Krishnamurty, P. Bannerman et al., A Smoothened receptor agonist is neuroprotective and promotes regeneration after ischemic brain injury, Cell Death Dis, 1481.

J. Asai, H. Takenaka, K. F. Kusano, M. Ii, C. Luedemann et al., Topical sonic hedgehog gene therapy accelerates wound healing in diabetes by enhancing endothelial progenitor cell-mediated microvascular remodeling, Circulation, vol.113, pp.2413-2424, 2006.

K. F. Kusano, K. L. Allendoerfer, W. Munger, R. Pola, M. Bosch-marce et al., Sonic hedgehog induces arteriogenesis in diabetic vasa nervorum and restores function in diabetic neuropathy, Arter. Thromb. Vasc. Biol, vol.24, pp.2102-2107, 2004.

C. Bueno-betí, S. Novella, R. Soleti, A. Mompeón, L. Vergori et al., Microparticles Harboring Sonic Hedgehog Morphogen Improve the Vasculogenesis Capacity of Endothelial Progenitor Cells Derived from Myocardial Infarction Patients, Cardiovasc. Res, vol.115, pp.409-418, 2018.

K. J. Lavine, A. Kovacs, and D. M. Ornitz, Hedgehog signaling is critical for maintenance of the adult coronary vasculature in mice, J. Clin. Investig, vol.118, pp.2404-2414, 2008.

M. F. Bijlsma, P. J. Leenders, B. J. Janssen, M. P. Peppelenbosch, H. Cate et al., Endogenous hedgehog expression contributes to myocardial ischemia-reperfusion-induced injury, Exp. Biol. Med, vol.233, pp.989-996, 2008.

H. Kuroda, N. Kurio, T. Shimo, K. Matsumoto, M. Masui et al., Oral Squamous Cell Carcinoma-derived Sonic Hedgehog Promotes Angiogenesis, Anticancer Res, vol.37, pp.6731-6737, 2017.

L. Geng, K. C. Cuneo, M. K. Cooper, H. Wang, K. Sekhar et al., Hedgehog signaling in the murine melanoma microenvironment, Angiogenesis, vol.10, pp.259-267, 2007.

V. Agrawal, D. Y. Kim, and Y. G. Kwon, Hhip regulates tumor-stroma-mediated upregulation of tumor angiogenesis, Exp. Mol. Med, vol.49, 2017.

D. Cui, X. Chen, J. Yin, W. Wang, M. Lou et al., Aberrant activation of Hedgehog/Gli1 pathway on angiogenesis in gliomas, Neurol India, vol.60, pp.589-596, 2012.

D. Mauro, C. Rosa, R. D'amato, V. Ciciola, P. Servetto et al., Hedgehog signalling pathway orchestrates angiogenesis in triple-negative breast cancers, Br. J. Cancer, vol.116, pp.1425-1435, 2017.

Y. Li, Y. Liu, G. Wang, Y. Wang, and L. Guo, Cooperation of Indian Hedgehog and Vascular Endothelial Growth Factor in Tumor Angiogenesis and Growth in Human Hepatocellular Carcinomas, an Immunohistochemical Study, Appl. Immunohistochem. Mol. Morphol, 2018.

X. Cao, J. Geradts, M. W. Dewhirst, and H. W. Lo, Upregulation of VEGF-A and CD24 gene expression by the tGLI1 transcription factor contributes to the aggressive behavior of breast cancer cells, Oncogene, vol.31, pp.104-115, 2012.

X. Liao, M. K. Siu, C. W. Au, E. S. Wong, H. Y. Chan et al., Aberrant activation of hedgehog signaling pathway in ovarian cancers: Effect on prognosis, cell invasion and differentiation, Carcinogenesis, vol.30, pp.131-140, 2009.

H. Zhu, R. L. Carpenter, W. Han, and H. W. Lo, The GLI1 splice variant TGLI1 promotes glioblastoma angiogenesis and growth, Cancer Lett, vol.343, pp.51-61, 2014.

L. G. Harris, L. K. Pannell, S. Singh, R. S. Samant, and L. Shevde, Increased vascularity and spontaneous metastasis of breast cancer by hedgehog signaling mediated upregulation of cyr61, Oncogene, vol.31, pp.3370-3380, 2012.

L. De-faro-valverde, T. De-almeida-pereira, R. B. Dias, V. S. Guimaraes, E. A. Ramos et al., Macrophages and endothelial cells orchestrate tumor-associated angiogenesis in oral cancer via hedgehog pathway activation, Tumour Biol, vol.37, pp.9233-9241, 2016.

C. L. Olsen, P. P. Hsu, J. Glienke, G. M. Rubanyi, and A. R. Brooks, Hedgehog-interacting protein is highly expressed in endothelial cells but down-regulated during angiogenesis and in several human tumors, BMC Cancer, vol.4, p.43, 2004.

M. Yamazaki, K. Nakamura, Y. Mizukami, M. Ii, J. Sasajima et al., Sonic hedgehog derived from human pancreatic cancer cells augments angiogenic function of endothelial progenitor cells, Cancer Sci, vol.99, pp.1131-1138, 2008.

O. J. Becher, D. Hambardzumyan, E. I. Fomchenko, H. Momota, L. Mainwaring et al., Gli activity correlates with tumor grade in platelet-derived growth factor-induced gliomas, Cancer Res, vol.68, pp.2241-2249, 2008.

G. N. Yan, L. Yang, Y. F. Lv, Y. Shi, L. L. Shen et al., Endothelial cells promote stem-like phenotype of glioma cells through activating the Hedgehog pathway, J. Pathol, vol.234, pp.11-22, 2014.

Y. Lin, C. Liu, R. Kannagi, and R. Yang, Inhibition of Endothelial SCUBE2 (Signal Peptide-CUB-EGF Domain-Containing Protein 2), a Novel VEGFR2 (Vascular Endothelial Growth Factor Receptor 2) Coreceptor, Suppresses Tumor Angiogenesis, Arter. Thromb. Vasc. Biol, vol.38, pp.1202-1215, 2018.

X. Huaitong, F. Yuanyong, T. Yueqin, Z. Peng, S. Wei et al., Microvesicles releasing by oral cancer cells enhance endothelial cell angiogenesis via Shh/RhoA signaling pathway, Cancer Biol, vol.18, pp.783-791, 2017.

K. P. Olive, M. A. Jacobetz, C. J. Davidson, A. Gopinathan, D. Mcintyre et al., Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer, vol.324, pp.1457-1461, 2009.

A. D. Rhim, P. E. Oberstein, D. H. Thomas, E. T. Mirek, C. F. Palermo et al., Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma, Cancer Cell, vol.25, pp.735-747, 2014.

R. Chaudhuri, T. Straubinger, N. L. Pitoniak, R. F. Hylander, B. L. Repasky et al., Tumor-Priming Smoothened Inhibitor Enhances Deposition and Efficacy of Cytotoxic Nanoparticles in a Pancreatic Cancer Model, Mol. Cancer, vol.15, pp.84-93, 2016.

F. Wang, F. Chen, Y. Shang, Y. Li, Z. Wang et al., Insulin resistance adipocyte-derived exosomes aggravate atherosclerosis by increasing vasa vasorum angiogenesis in diabetic ApoE-/-mice, Int. J. Cardiol, vol.265, pp.181-187, 2018.

H. He, H. Zhang, B. Li, G. Li, and Z. Wang, Blockade of the sonic hedgehog signalling pathway inhibits choroidal neovascularization in a laser-induced rat model, J. Huazhong Univ. Sci. Technol. Med. Sci, vol.30, pp.659-665, 2010.

G. Xie, S. S. Choi, W. Syn, G. A. Michelotti, M. Swiderska et al., Hedgehog signalling regulates liver sinusoidal endothelial cell capillarisation, Gut, vol.62, pp.299-309, 2013.

J. Yi, Y. Zhu, Y. Jia, H. Jiang, X. Zheng et al., The Annexin a2 Promotes Development in Arthritis through Neovascularization by Amplification Hedgehog Pathway, PLoS ONE, vol.11, 2016.

Y. Wang, S. Jin, Y. Sonobe, Y. Cheng, H. Horiuchi et al., Interleukin-1? Induces Blood-Brain Barrier Disruption by Downregulating Sonic Hedgehog in Astrocytes, PLoS ONE, vol.9, 2014.

S. Brilha, C. W. Ong, B. Weksler, N. Romero, P. Couraud et al., Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an in vitro model of CNS tuberculosis, Sci. Rep, 2017.

C. Podjaski, J. I. Alvarez, L. Bourbonniere, S. Larouche, S. Terouz et al., Netrin 1 regulates blood-brain barrier function and neuroinflammation, Brain, vol.138, pp.1598-1612, 2015.

C. Caradu, T. Couffinhal, C. Chapouly, S. Guimbal, P. Hollier et al., Restoring Endothelial Function by Targeting Desert Hedgehog Downstream of Klf2 Improves Critical Limb Ischemia in Adults, Circ. Res, vol.123, pp.1053-1065, 2018.
URL : https://hal.archives-ouvertes.fr/inserm-02468834

Y. Xia, Q. He, Y. Li, S. Chen, M. Huang et al., Recombinant Human Sonic Hedgehog Protein Regulates the Expression of ZO-1 and Occludin by Activating Angiopoietin-1 in Stroke Damage, PLoS ONE, vol.8, 2013.

, Int. J. Mol. Sci, vol.20, pp.3076-3098, 2019.

V. B. Singh, M. V. Singh, S. Gorantla, L. Y. Poluektova, and S. B. Maggirwar, Smoothened Agonist Reduces Human Immunodeficiency Virus Type-1-Induced Blood-Brain Barrier Breakdown in Humanized Mice, Sci. Rep, 2016.

V. B. Singh, M. V. Singh, D. Piekna-przybylska, S. Gorantla, L. Y. Poluektova et al., Sonic Hedgehog mimetic prevents leukocyte infiltration into the CNS during acute HIV infection, Sci. Rep, vol.7, p.9578, 2017.

R. V. Allahyari, K. L. Clark, K. A. Shepard, and A. D. Garcia, Sonic hedgehog signaling is negatively regulated in reactive astrocytes after forebrain stab injury, vol.9, 2019.

T. Li, J. Zhang, R. Y. Liu, Z. G. Lian, X. L. Chen et al., The role of the sonic hedgehog signaling pathway in early brain injury after experimental subarachnoid hemorrhage in rats, Neurosci. Lett, vol.552, pp.81-86, 2013.

H. Zhen, L. Zhao, Z. Ling, L. Kuo, X. Xue et al., Wip1 regulates blood-brain barrier function and neuro-inflammation induced by lipopolysaccharide via the sonic hedgehog signaling signaling pathway, Mol. Immunol, vol.93, pp.31-37, 2018.

X. Jiang, T. Chen, and X. Zhang, Activation of sonic hedgehog signaling attenuates oxidized low-density lipoprotein-stimulated brain microvascular endothelial cells dysfunction in vitro, Int. J. Clin. Exp. Pathol, vol.8, pp.12820-12828, 2015.

S. Azzi, L. Treps, H. M. Leclair, H. Ngo, E. Harford-wright et al., Desert Hedgehog/Patch2 Axis Contributes to Vascular Permeability and Angiogenesis in Glioblastoma, Front. Pharm, vol.6, p.281, 2015.
URL : https://hal.archives-ouvertes.fr/inserm-01247505

R. Soleti, T. Benameur, C. Porro, M. A. Panaro, R. Andriantsitohaina et al., Microparticles harboring Sonic Hedgehog promote angiogenesis through the upregulation of adhesion proteins and proangiogenic factors, Carcinogenesis, vol.30, pp.580-588, 2009.

C. Chapouly, Q. Yao, S. Vandierdonck, F. Larrieu-lahargue, J. N. Mariani et al., Impaired Hedgehog signalling-induced endothelial dysfunction is sufficient to induce neuropathy: Implication in diabetes, Cardiovasc. Res, vol.109, pp.217-227, 2016.
URL : https://hal.archives-ouvertes.fr/inserm-01777704

S. Sharghi-namini, M. Turmaine, C. Meier, V. Sahni, F. Umehara et al., The Structural and Functional Integrity of Peripheral Nerves Depends on the Glial-Derived Signal Desert Hedgehog, J. Neurosci, vol.26, pp.6364-6376, 2006.

N. Moreau, A. Mauborgne, S. Bourgoin, P. Couraud, I. A. Romero et al., Early alterations of Hedgehog signaling pathway in vascular endothelial cells after peripheral nerve injury elicit blood-nerve barrier disruption, nerve inflammation, and neuropathic pain development, Pain, vol.157, pp.827-839, 2016.

N. Moreau, W. Dieb, A. Mauborgne, S. Bourgoin, L. Villanueva et al., Hedgehog Pathway-Mediated Vascular Alterations Following Trigeminal Nerve Injury, J. Dent. Res, vol.96, pp.450-457, 2017.

Y. Yang, Q. Li, Z. Deng, Z. Zhang, J. Xu et al., Protection from lipopolysaccharide-induced pulmonary microvascular endothelial cell injury by activation of hedgehog signaling pathway, Mol. Biol. Rep, vol.38, pp.3615-3622, 2011.

H. Huang, J. He, D. Johnson, Y. Wei, Y. Liu et al., Deletion of placental growth factor prevents diabetic retinopathy and is associated with Akt activation and HIF1?-VEGF pathway inhibition, Diabetes, vol.64, pp.200-212, 2015.

A. Agouni, H. A. Mostefai, C. Porro, N. Carusio, J. Favre et al., Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release, FASEB J, vol.21, pp.2735-2741, 2007.

V. G. Marrachelli, M. L. Mastronardi, M. Sarr, R. Soleti, D. Leonetti et al., Sonic hedgehog carried by microparticles corrects angiotensin II-induced hypertension and endothelial dysfunction in mice, PLoS ONE, vol.8, 2013.

D. M. Nie, Q. L. Wu, P. Zheng, P. Chen, R. Zhang et al., Endothelial microparticles carrying hedgehog-interacting protein induce continuous endothelial damage in the pathogenesis of acute graft-versus-host disease, Am. J. Physiol. Cell Physiol, vol.310, pp.821-835, 2016.

, Int. J. Mol. Sci, vol.20, pp.3076-3099, 2019.

R. M. Farahani, B. Sarrafpour, M. Simonian, Q. Li, and N. Hunter, Directed glia-assisted angiogenesis in a mature neurosensory structure: Pericytes mediate an adaptive response in human dental pulp that maintains blood-barrier function, J. Comp. Neurol, vol.520, pp.3803-3826, 2012.

G. D. Dakubo, C. Mazerolle, M. Furimsky, C. Yu, B. St-jacques et al., Indian hedgehog signaling from endothelial cells is required for sclera and retinal pigment epithelium development in the mouse eye, Dev. Biol, vol.320, pp.242-255, 2008.

P. Chinchilla, L. Xiao, M. G. Kazanietz, and N. A. Riobo, Hedgehog proteins activate pro-angiogenic responses in endothelial cells through non-canonical signaling pathways, Cell Cycle, vol.9, pp.570-579, 2010.

Q. He, Y. Xia, S. Chen, Y. Wang, M. Huang et al., Astrocyte-derived sonic hedgehog contributes to angiogenesis in brain microvascular endothelial cells via RhoA/ROCK pathway after oxygen-glucose deprivation, Mol. Neurobiol, vol.47, pp.976-987, 2013.

A. H. Polizio, P. Chinchilla, X. Chen, S. Kim, D. R. Manning et al., Heterotrimeric Gi proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration, J. Biol. Chem, vol.286, pp.19589-19596, 2011.

S. Kanda, Y. Mochizuki, T. Suematsu, Y. Miyata, K. Nomata et al., Sonic hedgehog induces capillary morphogenesis by endothelial cells through phosphoinositide 3-kinase, J. Biol. Chem, vol.278, pp.8244-8249, 2003.

S. Kallakuri, J. A. Yu, J. Li, Y. Li, B. M. Weinstein et al., Endothelial cilia are essential for developmental vascular integrity in zebrafish, J. Am. Soc. Nephrol, vol.26, pp.864-875, 2015.

J. Roncalli, M. A. Renault, J. Tongers, S. Misener, T. Thorne et al., Sonic hedgehog-induced functional recovery after myocardial infarction is enhanced by AMD3100-mediated progenitor-cell mobilization, J. Am. Coll. Cardiol, vol.57, pp.2444-2452, 2011.

M. J. Frontini, Z. Nong, R. Gros, M. Drangova, C. O'neil et al., Fibroblast growth factor 9 delivery during angiogenesis produces durable, vasoresponsive microvessels wrapped by smooth muscle cells, Nat. Biotechnol, vol.29, pp.421-427, 2011.

J. K. Sicklick, Y. X. Li, S. S. Choi, Y. Qi, W. Chen et al., Role for hedgehog signaling in hepatic stellate cell activation and viability, Lab. Investig, vol.85, pp.1368-1380, 2005.

G. Wang, Z. Zhang, Z. Xu, H. Yin, L. Bai et al., Activation of the sonic hedgehog signaling controls human pulmonary arterial smooth muscle cell proliferation in response to hypoxia, Biochim. Biophys. Acta, pp.1359-1367, 2010.

H. Li, J. Li, Y. Li, P. Singh, L. Cao et al., Sonic hedgehog promotes autophagy of vascular smooth muscle cells, Am. J. Physiol. Heart Circ. Physiol, vol.303, pp.1319-1331, 2012.

D. Morrow, C. Sweeney, Y. A. Birney, S. Guha, N. Collins et al., Biomechanical regulation of hedgehog signaling in vascular smooth muscle cells in vitro and in vivo, Am. J. Physiol. Cell Physiol, vol.292, pp.488-496, 2007.

F. Li, M. Duman-scheel, D. Yang, W. Du, J. Zhang et al., Sonic hedgehog signaling induces vascular smooth muscle cell proliferation via induction of the G1 cyclin-retinoblastoma axis, Arter. Thromb. Vasc. Biol, vol.30, pp.1787-1794, 2010.

A. J. Doyle, E. M. Redmond, D. L. Gillespie, P. A. Knight, J. P. Cullen et al., Differential expression of Hedgehog/Notch and transforming growth factor-beta in human abdominal aortic aneurysms, J. Vasc. Surg, vol.62, pp.464-470, 2015.

D. Morrow, J. P. Cullen, W. Liu, S. Guha, C. Sweeney et al., Sonic Hedgehog induces Notch target gene expression in vascular smooth muscle cells via VEGF-A, Arter. Thromb. Vasc. Biol, vol.29, pp.1112-1118, 2009.

K. Chen, Q. J. Chen, L. J. Wang, Z. H. Liu, Q. Zhang et al., Increment of HFABP Level in Coronary Artery In-Stent Restenosis Segments in Diabetic and Nondiabetic Minipigs: HFABP Overexpression Promotes Multiple Pathway-Related Inflammation, Growth and Migration in Human Vascular Smooth Muscle Cells, J. Vasc. Res, vol.53, pp.27-38, 2016.

, Int. J. Mol. Sci, vol.20, pp.3076-3100, 2019.

Y. Shen, C. Li, R. Y. Zhang, Q. Zhang, W. F. Shen et al., Association of increased serum CTRP5 levels with in-stent restenosis after coronary drug-eluting stent implantation: CTRP5 promoting inflammation, migration and proliferation in vascular smooth muscle cells, Int. J. Cardiol, vol.228, pp.129-136, 2017.

E. Fitzpatrick, X. Han, W. Liu, E. Corcoran, D. Burtenshaw et al., Alcohol Reduces Arterial Remodeling by Inhibiting Sonic Hedgehog-Stimulated Stem Cell Antigen-1 Positive Progenitor Stem Cell Expansion, Alcohol Clin. Exp. Res, vol.41, pp.2051-2065, 2017.

C. J. Mooney, R. Hakimjavadi, E. Fitzpatrick, E. Kennedy, D. Walls et al., Hedgehog and Resident Vascular Stem Cell Fate, Stem Cells Int, vol.468428, 2015.

J. N. Passman, X. R. Dong, S. P. Wu, C. T. Maguire, K. A. Hogan et al., A sonic hedgehog signaling domain in the arterial adventitia supports resident Sca1+ smooth muscle progenitor cells, Proc. Natl. Acad. Sci, vol.105, pp.9349-9354, 2008.

H. Zhao, J. Feng, K. Seidel, S. Shi, O. Klein et al., Secretion of shh by a neurovascular bundle niche supports mesenchymal stem cell homeostasis in the adult mouse incisor, Cell Stem Cell, vol.14, pp.160-173, 2014.

Q. Zeng, B. Wei, Y. Zhao, X. Wang, Q. Fu et al., Shh mediates PDGF-induced contractile-to-synthetic phenotypic modulation in vascular smooth muscle cells through regulation of KLF4, Exp. Cell Res, vol.345, pp.82-92, 2016.

E. Dohle, S. Fuchs, M. Kolbe, A. Hofmann, H. Schmidt et al., Comparative study assessing effects of sonic hedgehog and VEGF in a human co-culture model for bone vascularisation strategies, Eur. Cell Mater, vol.21, pp.144-156, 2011.

S. W. Lee, M. A. Moskowitz, and J. R. Sims, Sonic hedgehog inversely regulates the expression of angiopoietin-1 and angiopoietin-2 in fibroblasts, Int. J. Mol. Med, vol.19, pp.445-451, 2007.

A. H. El-hashash, D. Al-alam, G. Turcatel, O. Rogers, X. Li et al., Six1 transcription factor is critical for coordination of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung, Dev. Biol, vol.353, pp.242-258, 2011.

A. H. El-hashash, D. Al-alam, G. Turcatel, S. Bellusci, and D. Warburton, Eyes absent 1 (Eya1) is a critical coordinator of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung, Dev. Biol, vol.350, pp.112-126, 2011.

H. Ali, N. Emoto, K. Yagi, N. Vignon-zellweger, K. Nakayama et al., Localization and characterization of a novel secreted protein, SCUBE2, in the development and progression of atherosclerosis, Kobe J. Med. Sci, vol.59, pp.122-131, 2013.

J. Dutzmann, A. Koch, S. Weisheit, K. Sonnenschein, L. Korte et al., Sonic hedgehog-dependent activation of adventitial fibroblasts promotes neointima formation, Cardiovasc. Res, vol.113, pp.1653-1663, 2017.

B. P. Herring, A. M. Hoggatt, S. L. Griffith, J. N. Mcclintick, and P. J. Gallagher, Inflammation and vascular smooth muscle cell dedifferentiation following carotid artery ligation, Physiol. Genom, vol.49, pp.115-126, 2017.

H. Teng, M. Chopp, A. Hozeska-solgot, L. Shen, M. Lu et al., Tissue plasminogen activator and plasminogen activator inhibitor 1 contribute to sonic hedgehog-induced in vitro cerebral angiogenesis, PLoS ONE, vol.7, 2012.

H. R. Maun, X. Wen, A. Lingel, F. J. De-sauvage, R. A. Lazarus et al., Hedgehog pathway antagonist 5E1 binds hedgehog at the pseudo-active site, J. Biol. Chem, vol.285, pp.26570-26580, 2010.

M. Vanlandewijck, L. He, M. A. Mae, J. Andrae, K. Ando et al., A molecular atlas of cell types and zonation in the brain vasculature, Nature, vol.554, pp.475-480, 2018.

, This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, © 2019 by the authors. Licensee MDPI