Impact of Notch Signaling on Inflammatory Responses in Cardiovascular Disorders

International Journal of Molecular Sciences - Tập 14 Số 4 - Trang 6863-6888
Thibaut Quillard1, Béatrice Charreau2
1Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. [email protected].
2University of Nantes

Tóm tắt

Notch signaling is a major pathway in cell fate decisions. Since the first reports showing the major role of Notch in embryonic development, a considerable and still growing literature further highlights its key contributions in various pathological processes during adult life. In particular, Notch is now considered as a major player in vascular homeostasis through the control of key cellular functions. In parallel, confounding evidence emerged that inflammatory responses regulate Notch signaling in vitro in endothelial cells, smooth muscle cells or vascular infiltrating cells and in vivo in vascular and inflammatory disorders and in cardiovascular diseases. This review presents how inflammation influences Notch in vascular cells and, reciprocally, emphasizes the functional role of Notch on inflammatory processes, notably by regulating key cell functions (differentiation, proliferation, apoptosis/survival, activation). Understanding how the disparity of Notch receptors and ligands impacts on vasculature biology remains critical for the design of relevant and adequate therapeutic strategies targeting Notch in this major pathological context.

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Tài liệu tham khảo

1994, Roles of the Notch gene in Drosophila wing morphogenesis, Mech. Dev, 46, 109, 10.1016/0925-4773(94)90080-9

Rand, 1999, Notch signaling: Cell fate control and signal integration in development, Science, 284, 770, 10.1126/science.284.5415.770

Weinmaster, 2010, Canonical and non-canonical Notch ligands, Curr. Top. Dev. Biol, 92, 73, 10.1016/S0070-2153(10)92003-6

Eiraku, 2005, DNER acts as a neuron-specific Notch ligand during Bergmann glial development, Nat. Neurosci, 8, 873, 10.1038/nn1492

Hu, 2006, Cross-Talk between F3/contactin and Notch at axoglial interface: A role in oligodendrocyte development, Dev. Neurosci, 28, 25, 10.1159/000090750

Baladron, 2005, dlk acts as a negative regulator of Notch1 activation through interactions with specific EGF-like repeats, Exp. Cell Res, 303, 343, 10.1016/j.yexcr.2004.10.001

Bruckner, 2000, Glycosyltransferase activity of Fringe modulates Notch-Delta interactions, Nature, 406, 411, 10.1038/35019075

Hicks, 2000, Fringe differentially modulates Jagged1 and Delta1 signalling through Notch1 and Notch2, Nat. Cell Biol, 2, 515, 10.1038/35019553

Rampal, 2007, Notch signaling in normal and disease States: Possible therapies related to glycosylation, Curr. Mol. Med, 7, 427, 10.2174/156652407780831593

Vooijs, 2011, Proteolytic cleavage of Notch: “HIT and RUN”, Curr. Mol. Med, 11, 255, 10.2174/156652411795677972

Nakagawa, 2000, Members of the HRT family of basic helix-loop-helix proteins act as transcriptional repressors downstream of Notch signaling, Proc. Natl. Acad. Sci. USA, 97, 13655, 10.1073/pnas.250485597

Iso, 2003, HES and HERP families: Multiple effectors of the Notch signaling pathway, J. Cell Physiol, 194, 237, 10.1002/jcp.10208

Sprinzak, 2010, Cis-Interactions between Notch and Delta generate mutually exclusive signalling states, Nature, 465, 86, 10.1038/nature08959

Cohen, 2010, Dynamic filopodia transmit intermittent Delta-Notch signaling to drive pattern refinement during lateral inhibition, Dev. Cell, 19, 78, 10.1016/j.devcel.2010.06.006

Krebs, 2000, Notch signaling is essential for vascular morphogenesis in mice, Genes Dev, 14, 1343, 10.1101/gad.14.11.1343

Uyttendaele, 1996, Notch4/int-3, a mammary proto-oncogene, is an endothelial cell-specific mammalian Notch gene, Development, 122, 2251, 10.1242/dev.122.7.2251

Shawber, 2004, Notch function in the vasculature: Insights from zebrafish, mouse and man, Bioessays, 26, 225, 10.1002/bies.20004

Duarte, 2004, Dosage-Sensitive requirement for mouse Dll4 in artery development, Genes Dev, 18, 2474, 10.1101/gad.1239004

Gale, 2004, Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to major defects in arterial and vascular development, Proc. Natl. Acad. Sci. USA, 101, 15949, 10.1073/pnas.0407290101

Mailhos, 2001, Delta4, an endothelial specific notch ligand expressed at sites of physiological and tumor angiogenesis, Differentiation, 69, 135, 10.1046/j.1432-0436.2001.690207.x

Uyttendaele, 2001, Vascular patterning defects associated with expression of activated Notch4 in embryonic endothelium, Proc. Natl. Acad. Sci. USA, 98, 5643, 10.1073/pnas.091584598

Miele, 2006, Notch signaling in cancer, Curr. Mol. Med, 6, 905, 10.2174/156652406779010830

Thurston, 2007, The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth, Nat. Rev. Cancer, 7, 327, 10.1038/nrc2130

Marchant, 2012, Inflammation in myocardial diseases, Circ. Res, 110, 126, 10.1161/CIRCRESAHA.111.243170

Frangogiannis, 2008, The immune system and cardiac repair, Pharmacol. Res, 58, 88, 10.1016/j.phrs.2008.06.007

Takeshita, 2007, Critical role of endothelial Notch1 signaling in postnatal angiogenesis, Circ. Res, 100, 70, 10.1161/01.RES.0000254788.47304.6e

Kratsios, 2010, Distinct roles for cell-autonomous Notch signaling in cardiomyocytes of the embryonic and adult heart, Circ. Res, 106, 559, 10.1161/CIRCRESAHA.109.203034

Li, 2009, Smooth muscle Notch1 mediates neointimal formation after vascular injury, Circulation, 119, 2686, 10.1161/CIRCULATIONAHA.108.790485

LaFramboise, 2005, Molecular dynamics of the compensatory response to myocardial infarct, J. Mol. Cell Cardiol, 38, 103, 10.1016/j.yjmcc.2004.09.011

Croquelois, 2008, Control of the adaptive response of the heart to stress via the Notch1 receptor pathway, J. Exp. Med, 205, 3173, 10.1084/jem.20081427

Russell, 2011, A dynamic notch injury response activates epicardium and contributes to fibrosis repair, Circ. Res, 108, 51, 10.1161/CIRCRESAHA.110.233262

Li, 2011, Notch1 in bone marrow-derived cells mediates cardiac repair after myocardial infarction, Circulation, 123, 866, 10.1161/CIRCULATIONAHA.110.947531

Libby, 2012, Inflammation in atherosclerosis, Arterioscler. Thromb. Vasc. Biol, 32, 2045, 10.1161/ATVBAHA.108.179705

Fung, 2007, Delta-Like 4 induces notch signaling in macrophages: Implications for inflammation, Circulation, 115, 2948, 10.1161/CIRCULATIONAHA.106.675462

Monsalve, 2006, Notch-1 up-regulation and signaling following macrophage activation modulates gene expression patterns known to affect antigen-presenting capacity and cytotoxic activity, J. Immunol, 176, 5362, 10.4049/jimmunol.176.9.5362

Aoyama, 2009, Gamma-Secretase inhibitor reduces diet-induced atherosclerosis in apolipoprotein E-deficient mice, Biochem. Biophys. Res. Commun, 383, 216, 10.1016/j.bbrc.2009.03.154

Fukuda, 2012, Notch ligand Delta-like 4 blockade attenuates atherosclerosis and metabolic disorders, Proc. Natl. Acad. Sci. USA, 109, E1868, 10.1073/pnas.1116889109

Hellstrom, 2007, Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis, Nature, 445, 776, 10.1038/nature05571

Kwon, 2009, The role of notch signaling in endothelial progenitor cell biology, Trends Cardiovasc. Med, 19, 170, 10.1016/j.tcm.2009.10.002

Schmauss, 2008, Cardiac allograft vasculopathy: Recent developments, Circulation, 117, 2131, 10.1161/CIRCULATIONAHA.107.711911

Quillard, 2008, Impaired Notch4 activity elicits endothelial cell activation and apoptosis: Implication for transplant arteriosclerosis, Arterioscler. Thromb. Vasc. Biol, 28, 2258, 10.1161/ATVBAHA.108.174995

Ando, 2003, Induction of Notch signaling by tumor necrosis factor in rheumatoid synovial fibroblasts, Oncogene, 22, 7796, 10.1038/sj.onc.1206965

Quillard, 2010, Inflammation dysregulates Notch signaling in endothelial cells: Implication of Notch2 and Notch4 to endothelial dysfunction, Biochem. Pharmacol, 80, 2032, 10.1016/j.bcp.2010.07.010

Fernandez, 2008, Tumor necrosis factor-alpha and endothelial cells modulate Notch signaling in the bone marrow microenvironment during inflammation, Exp. Hematol, 36, 545, 10.1016/j.exphem.2007.12.012

Joutel, 2000, The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients, J. Clin. Invest, 105, 597, 10.1172/JCI8047

Aguilera, 2004, Recruitment of IkappaBalpha to the hes1 promoter is associated with transcriptional repression, Proc. Natl. Acad. Sci. USA, 101, 16537, 10.1073/pnas.0404429101

Clement, 2007, Notch3 and IL-1beta exert opposing effects on a vascular smooth muscle cell inflammatory pathway in which NF-kappaB drives crosstalk, J. Cell Sci, 120, 3352, 10.1242/jcs.007872

Espinosa, 2003, IkappaBalpha and p65 regulate the cytoplasmic shuttling of nuclear corepressors: Cross-Talk between Notch and NFkappaB pathways, Mol. Biol. Cell, 14, 491, 10.1091/mbc.e02-07-0404

Pucci, 2009, A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood “resident” monocytes, and embryonic macrophages suggests common functions and developmental relationships, Blood, 114, 901, 10.1182/blood-2009-01-200931

Fantin, 2010, Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction, Blood, 116, 829, 10.1182/blood-2009-12-257832

Armulik, 2011, Pericytes: Developmental, physiological, and pathological perspectives, problems, and promises, Dev. Cell, 21, 193, 10.1016/j.devcel.2011.07.001

Kim, 2008, Downregulation by lipopolysaccharide of Notch signaling, via nitric oxide, J. Cell Sci, 121, 1466, 10.1242/jcs.019018

Monsalve, 2009, Notch1 upregulates LPS-induced macrophage activation by increasing NF-kappaB activity, Eur. J. Immunol, 39, 2556, 10.1002/eji.200838722

Palaga, 2008, Notch signaling is activated by TLR stimulation and regulates macrophage functions, Eur. J. Immunol, 38, 174, 10.1002/eji.200636999

Mosser, 2008, Exploring the full spectrum of macrophage activation, Nat. Rev. Immunol, 8, 958, 10.1038/nri2448

Xu, 2012, Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization, Nat. Immunol, 13, 642, 10.1038/ni.2304

Gentle, 2012, Noncanonical Notch signaling modulates cytokine responses of dendritic cells to inflammatory stimuli, J. Immunol, 189, 1274, 10.4049/jimmunol.1103102

Kassner, 2010, Cutting edge: Plasmacytoid dendritic cells induce IL-10 production in T cells via the Delta-like-4/Notch axis, J. Immunol, 184, 550, 10.4049/jimmunol.0903152

Woollard, 2010, Monocytes in atherosclerosis: Subsets and functions, Nat. Rev. Cardiol, 7, 77, 10.1038/nrcardio.2009.228

Piggott, 2011, Blocking the NOTCH Pathway inhibits vascular inflammation in large-vessel vasculitis, Circulation, 123, 309, 10.1161/CIRCULATIONAHA.110.936203

Outtz, 2010, Notch1 deficiency results in decreased inflammation during wound healing and regulates vascular endothelial growth factor receptor-1 and inflammatory cytokine expression in macrophages, J. Immunol, 185, 4363, 10.4049/jimmunol.1000720

Zen, 2010, Inhibition of delta-like-4-mediated signaling impairs reparative angiogenesis after ischemia, Circ. Res, 107, 283, 10.1161/CIRCRESAHA.110.221663

Noseda, 2004, Notch activation results in phenotypic and functional changes consistent with endothelial-to-mesenchymal transformation, Circ. Res, 94, 910, 10.1161/01.RES.0000124300.76171.C9

Sweeney, 2004, Notch 1 and 3 receptor signaling modulates vascular smooth muscle cell growth, apoptosis, and migration via a CBF-1/RBP-Jk dependent pathway, FASEB J, 18, 1421, 10.1096/fj.04-1700fje

Morrow, 2008, Notch and vascular smooth muscle cell phenotype, Circ. Res, 103, 1370, 10.1161/CIRCRESAHA.108.187534

Proweller, 2005, Notch signaling represses myocardin-induced smooth muscle cell differentiation, J. Biol. Chem, 280, 8994, 10.1074/jbc.M413316200

Noseda, 2006, Smooth muscle alpha-actin is a direct target of Notch/CSL, Circ. Res, 98, 1468, 10.1161/01.RES.0000229683.81357.26

Tang, 2008, Hairy-Related transcription factors inhibit Notch-induced smooth muscle alpha-actin expression by interfering with Notch intracellular domain/CBF-1 complex interaction with the CBF-1-binding site, Circ. Res, 102, 661, 10.1161/CIRCRESAHA.107.165134

Liu, 2006, Inhibition of endothelial cell proliferation by Notch1 signaling is mediated by repressing MAPK and PI3K/Akt pathways and requires MAML1, FASEB J, 20, 1009, 10.1096/fj.05-4880fje

Noseda, 2004, Notch activation induces endothelial cell cycle arrest and participates in contact inhibition: Role of p21Cip1 repression, Mol. Cell Biol, 24, 8813, 10.1128/MCB.24.20.8813-8822.2004

Benedito, 2008, Loss of Notch signalling induced by Dll4 causes arterial calibre reduction by increasing endothelial cell response to angiogenic stimuli, BMC Dev. Biol, 8, 117, 10.1186/1471-213X-8-117

Chen, 2009, Influence of Delta-like ligand 4/Notch signal transduction pathway upon the biological behavior of human umbilical vein endothelial cells, Zhonghua Yi Xue Za Zhi, 89, 3106

Hanahan, 1996, Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis, Cell, 86, 353, 10.1016/S0092-8674(00)80108-7

Hobson, 1984, Endothelial proliferation in tumours and normal tissues: Continuous labelling studies, Br. J. Cancer, 49, 405, 10.1038/bjc.1984.66

Emuss, 2009, KSHV manipulates Notch signaling by DLL4 and JAG1 to alter cell cycle genes in lymphatic endothelia, PLoS Pathog, 5, e1000616, 10.1371/journal.ppat.1000616

Campos, 2002, Determinants of Notch-3 receptor expression and signaling in vascular smooth muscle cells: Implications in cell-cycle regulation, Circ. Res, 91, 999, 10.1161/01.RES.0000044944.99984.25

Sakata, 2004, Drosophila Nedd4 regulates endocytosis of notch and suppresses its ligand-independent activation, Curr. Biol, 14, 2228, 10.1016/j.cub.2004.12.028

Wang, 2003, HRT1 modulates vascular smooth muscle cell proliferation and apoptosis, Biochem. Biophys. Res. Commun, 308, 596, 10.1016/S0006-291X(03)01453-0

Leong, 2002, Activated Notch4 inhibits angiogenesis: Role of beta 1-integrin activation, Mol. Cell Biol, 22, 2830, 10.1128/MCB.22.8.2830-2841.2002

Ferran, 2006, Protective genes in the vessel wall: Modulators of graft survival and function, Transplantation, 82, S36, 10.1097/01.tp.0000231445.62162.d5

Terraube, 2009, Factor VIII and von Willebrand factor interaction: Biological, clinical and therapeutic importance, Haemophilia, 16, 3, 10.1111/j.1365-2516.2009.02005.x

MacKenzie, 2004, Notch4 inhibits endothelial apoptosis via RBP-Jkappa-dependent and -independent pathways, J. Biol. Chem, 279, 11657, 10.1074/jbc.M312102200

Quillard, 2009, Notch2 signaling sensitizes endothelial cells to apoptosis by negatively regulating the key protective molecule survivin, PLoS One, 4, e8244, 10.1371/journal.pone.0008244

Wang, 2002, Coordinate Notch3-hairy-related transcription factor pathway regulation in response to arterial injury. Mediator role of platelet-derived growth factor and ERK, J. Biol. Chem, 277, 23165, 10.1074/jbc.M201409200

Heitzler, 2010, Biodiversity and noncanonical Notch signaling, Curr. Top. Dev. Biol, 92, 457, 10.1016/S0070-2153(10)92014-0

Cheng, 2001, Notch-1 regulates NF-kappaB activity in hemopoietic progenitor cells, J. Immunol, 167, 4458, 10.4049/jimmunol.167.8.4458

Shin, 2006, Notch1 augments NF-kappaB activity by facilitating its nuclear retention, EMBO J, 25, 129, 10.1038/sj.emboj.7600902

Schwarzer, 2011, Notch and NF-kappaB signaling pathways in the biology of classical Hodgkin lymphoma, Curr. Mol. Med, 11, 236, 10.2174/156652411795243423

Wang, 2001, Human Notch-1 inhibits NF-kappa B activity in the nucleus through a direct interaction involving a novel domain, J. Immunol, 167, 289, 10.4049/jimmunol.167.1.289

Oakley, 2003, Basal expression of IkappaBalpha is controlled by the mammalian transcriptional repressor RBP-J (CBF1) and its activator Notch1, J. Biol. Chem, 278, 24359, 10.1074/jbc.M211051200

Ang, 2007, Notch and NFkappaB signaling pathways: Do they collaborate in normal vertebrate brain development and function?, Bioessays, 29, 1039, 10.1002/bies.20647

Johnston, 2009, TNF induction of jagged-1 in endothelial cells is NFkappaB-dependent, Gene, 435, 36, 10.1016/j.gene.2009.01.003

Frantz, 2007, Mechanisms of disease: Toll-Like receptors in cardiovascular disease, Nat. Clin. Pract. Cardiovasc. Med, 4, 444, 10.1038/ncpcardio0938

Raymond, 2007, Toll-Like receptors, Notch ligands, and cytokines drive the chronicity of lung inflammation, Proc. Am. Thorac. Soc, 4, 635, 10.1513/pats.200706-067TH

Henke, 2011, Toll-Like receptor 9 signaling is critical for early experimental deep vein thrombosis resolution, Arterioscler. Thromb. Vasc. Biol, 31, 43, 10.1161/ATVBAHA.110.216317

Schaller, 2007, Notch ligand Delta-like 4 regulates disease pathogenesis during respiratory viral infections by modulating Th2 cytokines, J. Exp. Med, 204, 2925, 10.1084/jem.20070661

Ito, 2009, TLR9 regulates the mycobacteria-elicited pulmonary granulomatous immune response in mice through DC-derived Notch ligand delta-like 4, J. Clin. Invest, 119, 33

Zhang, 2012, Notch signal suppresses Toll-like receptor-triggered inflammatory responses in macrophages by inhibiting extracellular signal-regulated kinase 1/2-mediated nuclear factor kappaB activation, J. Biol. Chem, 287, 6208, 10.1074/jbc.M111.310375

Gustafsson, 2005, Hypoxia requires notch signaling to maintain the undifferentiated cell state, Dev. Cell, 9, 617, 10.1016/j.devcel.2005.09.010

Sahlgren, 2008, Notch signaling mediates hypoxia-induced tumor cell migration and invasion, Proc. Natl. Acad. Sci. USA, 105, 6392, 10.1073/pnas.0802047105

Semenza, 2010, Vascular responses to hypoxia and ischemia, Arterioscler. Thromb. Vasc. Biol, 30, 648, 10.1161/ATVBAHA.108.181644

Hulten, 2009, The role of hypoxia in atherosclerosis, Curr. Opin. Lipidol, 20, 409, 10.1097/MOL.0b013e3283307be8

Diez, 2007, Hypoxia-Mediated activation of Dll4-Notch-Hey2 signaling in endothelial progenitor cells and adoption of arterial cell fate, Exp. Cell Res, 313, 1, 10.1016/j.yexcr.2006.09.009

Patel, 2005, Up-Regulation of delta-like 4 ligand in human tumor vasculature and the role of basal expression in endothelial cell function, Cancer Res, 65, 8690, 10.1158/0008-5472.CAN-05-1208

Pietras, 2011, JAG2 induction in hypoxic tumor cells alters Notch signaling and enhances endothelial cell tube formation, Mol. Cancer Res, 9, 626, 10.1158/1541-7786.MCR-10-0508

Li, 2009, Notch3 signaling promotes the development of pulmonary arterial hypertension, Nat. Med, 15, 1289, 10.1038/nm.2021

Coleman, 2009, Signalling cross talk of the HIF system: Involvement of the FIH protein, Curr. Pharm. Des, 15, 3904, 10.2174/138161209789649448

Zheng, 2008, Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways, Proc. Natl. Acad. Sci. USA, 105, 3368, 10.1073/pnas.0711591105

Timmerman, 2004, Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation, Genes Dev, 18, 99, 10.1101/gad.276304

Zavadil, 2004, Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition, EMBO J, 23, 1155, 10.1038/sj.emboj.7600069

Mount, 2007, Regulation of endothelial and myocardial NO synthesis by multi-site eNOS phosphorylation, J. Mol. Cell Cardiol, 42, 271, 10.1016/j.yjmcc.2006.05.023

Garg, 2005, Mutations in NOTCH1 cause aortic valve disease, Nature, 437, 270, 10.1038/nature03940

Feng, 2002, Development of heart failure and congenital septal defects in mice lacking endothelial nitric oxide synthase, Circulation, 106, 873, 10.1161/01.CIR.0000024114.82981.EA

Forstermann, 2010, Nitric oxide and oxidative stress in vascular disease, Pflugers Arch, 459, 923, 10.1007/s00424-010-0808-2

Chang, 2011, Notch initiates the endothelial-to-mesenchymal transition in the atrioventricular canal through autocrine activation of soluble guanylyl cyclase, Dev. Cell, 21, 288, 10.1016/j.devcel.2011.06.022

Grandbarbe, 2007, Notch signaling modulates the activation of microglial cells, Glia, 55, 1519, 10.1002/glia.20553

Charles, 2010, Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells, Cell Stem Cell, 6, 141, 10.1016/j.stem.2010.01.001

Ishimura, 2005, Inducible nitric oxide synthase up-regulates Notch-1 in mouse cholangiocytes: Implications for carcinogenesis, Gastroenterology, 128, 1354, 10.1053/j.gastro.2005.01.055

Morga, 2009, Jagged1 regulates the activation of astrocytes via modulation of NFkappaB and JAK/STAT/SOCS pathways, Glia, 57, 1741, 10.1002/glia.20887

Leask, 2010, Potential therapeutic targets for cardiac fibrosis: TGFbeta, angiotensin, endothelin, CCN2, and PDGF, partners in fibroblast activation, Circ. Res, 106, 1675, 10.1161/CIRCRESAHA.110.217737

Derynck, 2003, Smad-Dependent and Smad-independent pathways in TGF-beta family signalling, Nature, 425, 577, 10.1038/nature02006

Blokzijl, 2003, Cross-Talk between the Notch and TGF-beta signaling pathways mediated by interaction of the Notch intracellular domain with Smad3, J. Cell Biol, 163, 723, 10.1083/jcb.200305112

Itoh, 2004, Synergy and antagonism between Notch and BMP receptor signaling pathways in endothelial cells, EMBO J, 23, 541, 10.1038/sj.emboj.7600065

Fu, 2009, Differential regulation of transforming growth factor beta signaling pathways by Notch in human endothelial cells, J. Biol. Chem, 284, 19452, 10.1074/jbc.M109.011833

Tang, 2010, Notch and transforming growth factor-beta (TGFbeta) signaling pathways cooperatively regulate vascular smooth muscle cell differentiation, J. Biol. Chem, 285, 17556, 10.1074/jbc.M109.076414

Kennard, 2008, Transforming growth factor-beta (TGF-1) down-regulates Notch3 in fibroblasts to promote smooth muscle gene expression, J. Biol. Chem, 283, 1324, 10.1074/jbc.M706651200

Doi, 2009, Notch signaling regulates the differentiation of bone marrow-derived cells into smooth muscle-like cells during arterial lesion formation, Biochem. Biophys. Res. Commun, 381, 654, 10.1016/j.bbrc.2009.02.116

Moloney, 2000, Fringe is a glycosyltransferase that modifies Notch, Nature, 406, 369, 10.1038/35019000

Garg, 2006, Molecular genetics of aortic valve disease, Curr. Opin. Cardiol, 21, 180, 10.1097/01.hco.0000221578.18254.70

McDaniell, 2006, NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway, Am. J. Hum. Genet, 79, 169, 10.1086/505332

Li, 1997, Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1, Nat. Genet, 16, 243, 10.1038/ng0797-243

Peters, 2008, Enhanced l-arginine-induced vasoreactivity suggests endothelial dysfunction in CADASIL, J. Neurol, 255, 1203, 10.1007/s00415-008-0876-9

Ridgway, 2006, Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis, Nature, 444, 1083, 10.1038/nature05313

Scehnet, 2007, Inhibition of Dll4-mediated signaling induces proliferation of immature vessels and results in poor tissue perfusion, Blood, 109, 4753, 10.1182/blood-2006-12-063933

Moellering, 2009, Direct inhibition of the NOTCH transcription factor complex, Nature, 462, 182, 10.1038/nature08543

Zhang, 2010, Characterization of Notch1 antibodies that inhibit signaling of both normal and mutated Notch1 receptors, PLoS One, 5, e9094, 10.1371/journal.pone.0009094

Yan, 2010, Chronic DLL4 blockade induces vascular neoplasms, Nature, 463, E6, 10.1038/nature08751