Shear stress, arterial identity and atherosclerosis

Summary

In the developing embryo, the vasculature first takes the form of a web-like network called the vascular plexus. Arterial and venous differentiation is subsequently guided by the specific expression of genes in the endothelial cells that provide spatial and temporal cues for development. Notch1/4, Notch ligand delta-like 4 (Dll4), and Notch downstream effectors are typically expressed in arterial cells along with EphrinB2, whereas chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and EphB4 characterise vein endothelial cells. Haemodynamic forces (blood pressure and blood flow) also contribute importantly to vascular remodelling. Early arteriovenous differentiation and local blood flow may hold the key to future inflammatory diseases. Indeed, despite the fact that atherosclerosis risk factors such as smoking, hypertension, hypercholesterolaemia, and diabetes all induce endothelial cell dysfunction throughout the vasculature, plaques develop only in arteries, and they localise essentially in vessel branch points, curvatures and bifurcations, where blood flow (and consequently shear stress) is low or oscillatory. Arterial segments exposed to high blood flow (and high laminar shear stress) tend to remain plaque-free. These observations have led many to investigate what particular properties of arterial or venous endothelial cells confer susceptibility or protection from plaque formation, and how that might interact with a particular shear stress environment.

Keywords

Shear stress - endothelial cells - arteriovenous differentiation - atherosclerosis

• References

• 1 Tabas I. Apoptosis and efferocytosis in mouse models of atherosclerosis. Curr Drug Targets 2007; 8: 1288-1296.
• 2 Lusis AJ. Atherosclerosis. Nature 2000; 407: 233-241.
• 3 Bobryshev YV, Watanabe T. Subset of vascular dendritic cells transforming into foam cells in human atherosclerotic lesions. Cardiovasc Pathol 1997; 6: 321-331.
• 4 Paulson KE. et al. Resident intimal dendritic cells accumulate lipid and contribute to the initiation of atherosclerosis. Circ Res 2010; 106: 383-390.
• 5 Weber C. Frontiers of vascular biology: mechanisms of inflammation and immunoregulation during arterial remodelling. Thromb Haemost 2009; 102: 188-190.
• 6 Virmani R. et al. Pathology of the vulnerable plaque. J Am Coll Cardiol 2006; 47 (Suppl. 08) C13-18.
• 7 Kawahara T. et al. Atorvastatin, etidronate, or both in patients at high risk for atherosclerotic aortic plaques: a randomized, controlled trial. Circulation 2013; 127: 2327-2335.
• 8 Robbins CS. et al. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat Med 2013; 19: 1166-1172.
• 9 Hegele RA. et al. Nonstatin Low-Density Lipoprotein-Lowering Therapy and Cardiovascular Risk Reduction-Statement From ATVB Council. Arterioscler Thromb Vasc Biol. 2015 Epub ahead of print.
• 10 Gimbrone MA. et al. Biomechanical activation: An emerging paradigm in endothelial adhesion biology. J Clin Invest 1997; 99: 1809-1813.
• 11 Traub O, Berk BC. Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force. Arterioscler Thromb Vasc Biol 1998; 18: 677-685.
• 12 Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 2000; 87: 840-844.
• 13 Caro CG. et al. Arterial wall shear and distribution of early atheroma in man. Nature 1969; 223: 1159-1160.
• 14 Malek AM, Alper SL, Izumo S. Haemodynamic shear stress and its role in atherosclerosis. J Am Med Assoc 1999; 282: 2035-2042.
• 15 Davies PF. et al. The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress regions in vivo. Cardiovasc Res 2013; 99: 315-327.
• 16 Chatzizisis YS. et al. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodelling: molecular, cellular, and vascular behavior. J Am Coll Cardiol 2007; 49: 2379-2393.
• 17 Lehoux S. et al. Molecular mechanisms of the vascular responses to haemody-namic forces. J Intern Med 2006; 259 (04) 381-92.
• 18 Hajra L. et al. The NFkB signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc Natl Acad Sci USA 2000; 97: 9052-9057.
• 19 Dimmeler S. et al. Upregulation of superoxide dismutase and nitric oxide syn-thase mediates the apoptosis-suppressive effects of shear stress on endothelial cells. Arterioscler Thromb Vasc Biol 1999; 19: 656-664.
• 20 Yamawaki H. et al. Chronic physiological shear stress inhibits tumor necrosis factor-induced proinflammatory responses in rabbit aorta perfused ex vivo. Circulation 2003; 108: 1619-1625.
• 21 Risau W. Mechanisms of angiogenesis. Nature 1997; 386: 671-674.
• 22 Wang HU. et al. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 1998; 93: 741-753.
• 23 Adams RH. et al. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev 1999; 13: 295-306.
• 24 Chong DC. et al. Stepwise arteriovenous fate acquisition during mammalian vasculogenesis. Devel Dynam 2011; 240: 2153-2165.
• 25 Le Noble F. et al. Flow regulates arterial-venous differentiation in the chick embryo yolk sac. Development 2004; 131: 361-375.
• 26 Fish JE, Wythe JD. The molecular regulation of arteriovenous specification and maintenance. Devel Dynam 2015; 244: 391-409.
• 27 Corada M. et al. Signalling pathways in the specification of arteries and veins. Arterioscler Thromb Vasc Biol 2014; 34: 2372-2377.
• 28 Domigan CK, Iruela-Arispe ML. Recent advances in vascular development. Curr Opin Hematol 2012; 19: 176-183.
• 29 Gridley T. Notch signalling in the vasculature. Curr Topics Devel Biol 2010; 92: 277-309.
• 30 Artavanis-Tsakonas S. et al. Notch signalling: cell fate control and signal integration in development. Science 1999; 284: 770-776.
• 31 Dallman MJ. et al. Notch: control of lymphocyte differentiation in the periphery. Curr Opin Immunol 2005; 17: 259-266.
• 32 Borggrefe T, Oswald F. The Notch signalling pathway: transcriptional regulation at Notch target genes. Cellular and molecular life sciences : CMLS 2009; 66: 1631-1646.
• 33 Sivarapatna A. et al. Arterial specification of endothelial cells derived from human induced pluripotent stem cells in a biomimetic flow bioreactor. Biomaterials 2015; 53: 621-633.
• 34 Masumura T. et al. Shear stress increases expression of the arterial endothelial marker ephrinB2 in murine ES cells via the VEGF-Notch signalling pathways. Arterioscler Thromb Vasc Biol 2009; 29: 2125-2131.
• 35 Obi S. et al. Fluid shear stress induces arterial differentiation of endothelial progenitor cells. J Appl Physiol 2009; 106: 203-211.
• 36 Jahnsen ED. et al. Notch1 is pan-endothelial at the onset of flow and regulated by flow. PloS one 2015; 10: e0122622.
• 37 Tu J. et al. Notch1 and 4 signalling responds to an increasing vascular wall shear stress in a rat model of arteriovenous malformations. BioMed Res Internat 2014; 2014: 368082.
• 38 Sweet DT. et al. Endothelial Shc regulates arteriogenesis through dual control of arterial specification and inflammation via the notch and nuclear factor-kappa-light-chain-enhancer of activated B-cell pathways. Circ Res 2013; 113: 32-39.
• 39 Chouinard-Pelletier G. et al. Increased shear stress inhibits angiogenesis in veins and not arteries during vascular development. Angiogenesis 2013; 16: 71-83.
• 40 Ii M. et al. Notch signalling regulates endothelial progenitor cell activity during recovery from arterial injury in hypercholesterolemic mice. Circulation 2010; 121: 1104-1112.
• 41 Suzuki Y. et al. Arterial shear stress augments the differentiation of endothelial progenitor cells adhered to VEGF-bound surfaces. Biochem Biophys Res Com-mun 2012; 423: 91-97.
• 42 van Gils JM. et al. Endothelial Expression of Guidance Cues in Vessel Wall Homeostasis: Dysregulation Under Proatherosclerotic Conditions. Arterioscler Thromb Vasc Biol 2013; 33: 911-919.
• 43 Goettsch W. et al. Down-regulation of endothelial ephrinB2 expression by laminar shear stress. Endothelium 2004; 11: 259-265.
• 44 Berard X. et al. Role of haemodynamic forces in the ex vivo arterialisation of human saphenous veins. J Vasc Surg 2013; 57: 1371-1382.
• 45 Fancher TT. et al. Control of blood vessel identity: from embryo to adult. Ann Vasc Dis 2008; 1: 28-34.
• 46 Kudo FA. et al. Venous identity is lost but arterial identity is not gained during vein graft adaptation. Arterioscler Thromb Vasc Biol 2007; 27: 1562-1571.
• 47 Romero ME. et al. Neoatherosclerosis From a Pathologist’s Point of View. Arterioscler Thromb Vasc Biol 2015; 35: e43-49.
• 48 Riou S. et al. High pressure promotes monocyte adhesion to the vascular wall. Circ Res 2007; 100: 1226-1233.
• 49 Longchamp A. et al. The use of external mesh reinforcement to reduce intimal hyperplasia and preserve the structure of human saphenous veins. Biomaterials 2014; 35: 2588-2599.
• 50 Geenen IL. et al. Endothelial cells (ECs) for vascular tissue engineering: venous ECs are less thrombogenic than arterial ECs. J Tissue Engin Regen Med 2015; 9: 564-576.
• 51 Wu X. et al. COUP-TFII switches responses of venous endothelium to atherosclerotic factors through controlling the profile of various inherent genes expression. J Cell Biochem 2011; 112: 256-264.
• 52 Ramkhelawon B. et al. Shear Stress Regulates Angiotensin Type 1 Receptor Expression in Endothelial Cells. Circ Res 2009; 105: 869-875.
• 53 Zhou X. et al. Soluble Jagged-1 inhibits restenosis of vein graft by attenuating Notch signalling. Microvasc Res 2015; 100: 9-16.
• 54 Xiao YG. et al. gamma-Secretase inhibitor DAPT attenuates intimal hyperplasia of vein grafts by inhibition of Notch1 signalling. Lab Invest 2014; 94: 654-662.
• 55 Castillo-Diaz SA. et al. Extensive demethylation of normally hypermethylated CpG islands occurs in human atherosclerotic arteries. Intern J Mol Med 2010; 26: 691-700.
• 56 Pelisek J. et al. Neovascularisation and angiogenic factors in advanced human carotid artery stenosis. Circ J 2012; 76: 1274-1282.
• 57 Aoyama T. et al. gamma-Secretase inhibitor reduces diet-induced atherosclerosis in apolipoprotein E-deficient mice. Biochem Biophys Res Commun 2009; 383: 216-221.
• 58 Fukuda D. et al. Notch ligand delta-like 4 blockade attenuates atherosclerosis and metabolic disorders. Proc Natl Acad Sci USA 2012; 109: E1868-1877.
• 59 Hans CP. et al. Inhibition of Notch1 signalling reduces abdominal aortic aneu-rysm in mice by attenuating macrophage-mediated inflammation. Arterioscler Thromb Vasc Biol 2012; 32: 3012-3023.
• 60 Zheng YH. et al. Notch gamma-secretase inhibitor dibenzazepine attenuates an-giotensin II-induced abdominal aortic aneurysm in ApoE knockout mice by multiple mechanisms. PloS one 2013; 8: e83310.
• 61 Zou S. et al. Notch signalling in descending thoracic aortic aneurysm and dissection. PloS one 2012; 7: e52833.
• 62 Outtz HH. et al. 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 2010; 185: 4363-4373.
• 63 Gordon S. Alternative activation of macrophages. Nat Rev Immunol 2003; 3: 23-35.
• 64 Martinez FO. et al. Macrophage activation and polarisation. Front Biosci 2008; 13: 453-461.
• 65 Mantovani A. et al. Macrophage polarisation comes of age. Immunity 2005; 23: 344-346.
• 66 Tabas I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol 2010; 10: 36-46.
• 67 Xu W. et al. Dendritic cell and macrophage subsets in the handling of dying cells. Immunobiology 2006; 211: 567-575.
• 68 Trogan E. et al. Gene expression changes in foam cells and the role of chemokine receptor CCR7 during atherosclerosis regression in ApoE-deficient mice. Proc Natl Acad Sci USA 2006; 103: 3781-3786.
• 69 Singla RD. et al. Regulation of Notch 1 signalling in THP-1 cells enhances M2 macrophage differentiation. Am J Physiol Heart Circ Physiol 2014; 307: H1634-1642.
• 70 Koga JI. et al. Macrophage Notch Ligand Delta-Like 4 Promotes Vein Graft Lesion Development: Implications for the Treatment of Vein Graft Failure. Arte-rioscler Thromb Vasc Biol. 2015 Epub ahead of print.
• 71 Palaga T. et al. Notch signalling is activated by TLR stimulation and regulates macrophage functions. Eur J Immunol 2008; 38: 174-183.
• 72 Hu X. et al. Integrated regulation of Toll-like receptor responses by Notch and interferon-gamma pathways. Immunity 2008; 29: 691-703.
• 73 Monsalve E. et al. Notch1 upregulates LPS-induced macrophage activation by increasing NF-kappaB activity. Eur J Immunol 2009; 39: 2556-2570.
• 74 Fung E. et al. Delta-like 4 induces notch signalling in macrophages: implications for inflammation. Circulation 2007; 115: 2948-2956.
• 75 Shih YT. et al. beta(2)-Integrin and Notch-1 differentially regulate CD34(+)CD31(+) cell plasticity in vascular niches. Cardiovasc Res 2012; 96: 296-307.
• 76 Liu ZJ. et al. Notch activation induces endothelial cell senescence and pro-inflammatory response: implication of Notch signalling in atherosclerosis. Atherosclerosis 2012; 225: 296-303.
• 77 Theodoris CV. et al. Human disease modelling reveals integrated transcriptional and epigenetic mechanisms of NOTCH1 haploinsufficiency. Cell 2015; 160: 1072-1086.
• 78 Schober A. et al. MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1. Nat Med 2014; 20: 368-376.
• 79 Briot A, Iruela-Arispe ML. Blockade of specific NOTCH ligands: a new promising approach in cancer therapy. Cancer Discov 2015; 5: 112-114.
• 80 Al Haj Zen A. et al. Inhibition of delta-like-4-mediated signalling impairs repar-ative angiogenesis after ischemia. Circ Res 2010; 107: 283-293.
• 81 Gentle ME. et al. Noncanonical Notch signalling modulates cytokine responses of dendritic cells to inflammatory stimuli. J Immunol 2012; 189: 1274-1284.
• 82 Kim MY. et al. Downregulation by lipopolysaccharide of Notch signalling, via nitric oxide. J Cell Sci 2008; 121: 1466-1476.
• 83 Quillard T. et al. Impaired Notch4 activity elicits endothelial cell activation and apoptosis: implication for transplant arteriosclerosis. Arterioscler Thromb Vasc Biol 2008; 28: 2258-2265.
• 84 Quillard T. et al. Inflammation dysregulates Notch signalling in endothelial cells: implication of Notch2 and Notch4 to endothelial dysfunction. Biochem Pharmacol 2010; 80: 2032-2041.
• 85 Ivanov AI, Romanovsky AA. Putative dual role of ephrin-Eph receptor interactions in inflammation. IUBMB Life 2006; 58: 389-394.
• 86 Zamora DO. et al. Human leukocytes express ephrinB2 which activates micro-vascular endothelial cells. Cell Immunol 2006; 242: 99-109.
• 87 Braun J. et al. Endothelial cell ephrinB2-dependent activation of monocytes in arteriosclerosis. Arterioscler Thromb Vasc Biol 2011; 31: 297-305.
• 88 Liu H. et al. EphrinB-mediated reverse signalling controls junctional integrity and pro-inflammatory differentiation of endothelial cells. Thromb Haemost 2014; 112: 151-163.