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Review Article

The vascular endothelium: A regulator of arterial tone and interface for the immune system

, , & ORCID Icon
Pages 458-470 | Received 22 Aug 2017, Accepted 16 Oct 2017, Published online: 30 Oct 2017

References

  • Mulvany MJ, Aalkjaer C. Structure and function of small arteries. Physiol Rev. 1990;70:921–961.
  • Christensen KL, Mulvany MJ. Location of resistance arteries. J Vasc Res. 2001;38:1–12.
  • Segal SS. Regulation of blood flow in the microcirculation. Microcirculation. 2005;12:33–45.
  • Davis MJ, Hill MA, Kuo L. Local regulation of microvascular perfusion. In: Tuma RF, Duran WN, Ley K, editors. Handbook of physiology: microcirculation. Academic Press; 2008. pp. 161–284.
  • Bayliss WM. On the local reactions of the arterial wall to changes of internal pressure. J Physiol (Lond). 1902;28:220–231.
  • Johnson PC. The myogenic response. In: Bohr DF, Somylo AP, Sparks HV, editors. Handbook of physiology: the cardiovascular system, vascular smooth muscle. Vol. 2. American Physiological Society; 1980. pp. 409–442.
  • Davis MJ, Hill MA. Signaling mechanisms underlying the vascular myogenic response. Physiol Rev. 1999;79:387–423.
  • Pries AR, Kuebler W. Normal endothelium. Handbook of Experimental Pharmacology. 2006;176:1–40.
  • Sato M, Ohashi T. Biorheological views of endothelial cell responses to mechanical stimuli. Biorheology. 2005;42:421–441.
  • Aird WC. Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ Res. 2007;100:158–173.
  • Westcott EB, Segal SS. Perivascular innervation: a multiplicity of roles in vasomotor control and myoendothelial signaling. Microcirculation. 2013;20:217–238.
  • Saltin B, Mortensen SP. Inefficient functional sympatholysis is an overlooked cause of malperfusion in contracting skeletal muscle. J Physiol (Lond). 2012;590:6269–6275.
  • Hearon CM Jr, Dinenno FA. Regulation of skeletal muscle blood flow during exercise in ageing humans. J Physiol (Lond). 2016;594:2261–2273.
  • Nausch LW, Bonev AD, Heppner TJ, et al. Sympathetic nerve stimulation induces local endothelial Ca2+ signals to oppose vasoconstriction of mouse mesenteric arteries. Am J Physiol Heart Circ Physiol. 2012;302:H594–H602.
  • Garland CJ, Bagher P, Powell C, et al. Voltage-dependent Ca2+ entry into smooth muscle during contraction promotes endothelium-mediated feedback vasodilation in arterioles. Sci Signal. 2017;10:eaal3806.
  • Thomas GD. Functional sympatholysis in hypertension. Auton Neurosci. 2015;188:64–68.
  • Chistiakov DA, Orekhov AN, Bobryshev YV. Endothelial barrier and its abnormalities in cardiovascular disease. Front Physiol. 2015;6:365.
  • Tietz S, Engelhardt B. Brain barriers: crosstalk between complex tight junctions and adherens junctions. J Cell Biol. 2015;209:493–506.
  • Mehta D, Ravindran K, Kuebler WM. Novel regulators of endothelial barrier function. Am J Physiol Lung Cell Mol Physiol. 2014;307:L924–L935.
  • Phng LK, Gerhardt H. Angiogenesis: a team effort coordinated by Notch. Dev Cell. 2009;16:196–208.
  • Yuan S, Kevil CG. Nitric oxide and hydrogen sulfide regulation of ischemic vascular remodeling. Microcirculation. 2016;23:134–145.
  • Wragg JW, Durant S, McGettrick HM, et al. Shear stress regulated gene expression and angiogenesis in vascular endothelium. Microcirculation. 2014;21:290–300.
  • Cora D, Astanina E, Giraudo E, et al. Semaphorins in cardiovascular medicine. Trends Mol Med. 2014;20:589–598.
  • Félétou M, Vanhoutte PM. EDHF: an update. Clin Sci. 2009;117:139–155.
  • Edwards G, Félétou M, Weston AH. Endothelium-derived hyperpolarising factors and associated pathways: a synopsis. Pflugers Arch. 2010;459:863–879.
  • Grgic I, Kaistha A, Hoyer J, et al. Endothelial Ca2+-activated K+ channels in normal and impaired EDHF-dilator responses - relevance to cardiovascular pathologies and drug discovery. Br J Pharmacol. 2009;157:509–526.
  • Vanhoutte PM, Shimokawa H, Félétou M, et al. Endothelial dysfunction and vascular disease - a 30th anniversary update. Acta Physiol (Oxf). 2017;219:22–96.
  • Sheng J-Z, Braun AP. Small- and intermediate-conductance Ca2+-activated K+ channels directly control agonist-evoked nitric oxide synthesis in human vascular endothelial cells. Am J Physiol Cell Physiol. 2007;293:C458–C467.
  • Várnai P, Hunyady L, Balla T. STIM and Orai: the long-awaited constituents of store-operated calcium entry. TIPS. 2009;30:118–128.
  • Ruhle B, Trebak M. Emerging roles for native Orai Ca2+ channels in cardiovascular disease. Curr Top Membr. 2013;71:209–235.
  • Earley S, Brayden JE. Transient receptor potential channels in the vasculature. Physiol Rev. 2015;95:645–690.
  • Sullivan MN, Earley S. TRP channel Ca(2+) sparklets: fundamental signals underlying endothelium-dependent hyperpolarization. Am J Physiol, Cell Physiol. 2013;305:C999–C1008.
  • Ledoux J, Taylor MS, Bonev AD, et al. Functional architecture of inositol 1,4,5-trisphosphate signaling in restricted spaces of myoendothelial projections. Proc Natl Acad Sci USA. 2008;105:9627–9632.
  • Bagher P, Beleznai T, Kansui Y, et al. Low intravascular pressure activates endothelial cell TRPV4 channels, local Ca2+ events, and IKCa channels, reducing arteriolar tone. Proc Natl Acad Sci USA. 2012;109:18174–18179.
  • Sonkusare SK, Bonev AD, Ledoux J, et al. Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science. 2012;336:597–601.
  • Francis M, Waldrup JR, Qian X, et al. Functional tuning of intrinsic endothelial Ca2+ dynamics in swine coronary arteries. Circ Res. 2016;118:1078–1090.
  • Lückhoff A, Busse R. Calcium influx into endothelial cells and formation of endothelium-derived relaxing factor is controlled by the membrane potential. Pflugers Arch. 1990;416:305–311.
  • Busse R, Fichtner H, Lückhoff A, et al. Hyperpolarization and increased free calcium in acetylcholine-stimulated endothelial cells. Am J Physiol Heart Circ Physiol. 1988;255:H965–H969.
  • Busse R, Edwards G, Félétou M, et al. EDHF: bringing the concepts together. Trends Pharmacol Sci. 2002;23:374–380.
  • Burnham MP, Bychkov R, Félétou M, et al. Characterization of an apamin-sensitive small-conductance Ca2+-activated K+ channel in porcine coronary artery endothelium: relevance to EDHF. Br J Pharmacol. 2002;135:1133–1143.
  • Bychkov R, Burnham MP, Richards GR, et al. Characterization of a charybdotoxin-sensitive intermediate conductance Ca2+-activated K+ channel in porcine coronary endothelium: relevance to EDHF. Br J Pharmacol. 2002;137:1346–1354.
  • Sheng J-Z, Ella S, Davis MJ, et al. Openers of SKCa and IKCa channels enhance agonist-evoked endothelial nitric oxide synthesis and arteriolar dilation. FASEB J. 2009;23:1138–1145.
  • Kamouchi M, Droogmans G, Nilius B. Membrane potential as a modulator of the free intracellular Ca2+ concentration in agonist-activated endothelial cells. Gen Physiol Biophysics. 1999;18:199–208.
  • Stankevicius E, Lopez-Valverde V, Rivera L, et al. Combination of Ca2+-activated K + channel blockers inhibits acetylcholine-evoked nitric oxide release in rat superior mesenteric artery. Br J Pharmacol. 2006;149:560–572.
  • Dalsgaard T, Kroigaard C, Misfeldt M, et al. Openers of small conductance calcium-activated potassium channels selectively enhance NO-mediated bradykinin vasodilatation in porcine retinal arterioles. Br J Pharmacol. 2010;160:1496–1508.
  • Mishra RC, Wulff H, Cole WC, et al. A pharmacologic activator of endothelial KCa channels enhances coronary flow in the hearts of type 2 diabetic rats. J Mol Cell Cardiol. 2014;72:364–373.
  • Brondum E, Kold-Petersen H, Simonsen U, et al. NS309 restores EDHF-type relaxation in mesenteric small arteries from type 2 diabetic ZDF rats. Br J Pharmacol. 2010;159:154–165.
  • Damkjaer M, Nielsen G, Bodendiek S, et al. Pharmacological activation of KCa3.1/KCa2.3 channels produces endothelial hyperpolarization and lowers blood pressure in conscious dogs. Br J Pharmacol. 2012;165:223–234.
  • Mishra RC, Mitchell JR, Gibbons-Kroeker C, et al. A pharmacologic activator of endothelial KCa channels increases systemic conductance and reduces arterial pressure in an anesthetized pig model. Vasc Pharmacol. 2016;79:24–31.
  • Davies PF. Flow-mediated endothelial mechanotransduction. Physiol Rev. 1995;75:519–560.
  • Vanhoutte PM, Zhao Y, Xu A, et al. Thirty years of saying NO: sources, fate, actions, and misfortunes of the endothelium-derived vasodilator mediator. Circ Res. 2016;119:375–396.
  • Schubert R, Nelson MT. Protein kinases: tuners of the BKCa channel in smooth muscle. Trends Pharmacol Sci. 2001;22:505–512.
  • Kyle BD, Braun AP. The regulation of BK channel activity by pre- and post-translational modifications. Front Physiol. 2014;5:316.
  • McDonald LJ, Murad F. Nitric oxide and cGMP signaling. Adv Pharmacol. 1995;34:263–275.
  • Quayle JM, Nelson MT, Standen NB. ATP-sensitive and inwardly rectifying potassium channels in smooth muscle. Physiol Rev. 1997;77:1165–1232.
  • Chauhan SD, Nilsson H, Ahluwalia M, et al. Release of C-type natriuretic peptide accountf for the biological activity of endothelium-derived hyperpolarizing factor. Proc Natl Acad Sci USA. 2003;100:1426–1431.
  • Gauthier KM, Goldman DH, Aggarwal NT, et al. Role of arachidonic acid lipoxygenase metabolites in acetylcholine-induced relaxations of mouse arteries. Am J Physiol Heart Circ Physiol. 2011;300:H725–H735.
  • Campbell WB, Fleming I. Epoxyeicosatrienoic acide and endothelium-dependent responses. Pflugers Arch - Eur J Physiol. 2010;459:881–895.
  • Shimokawa H. Hydrogen peroxide as an endothelium-derived hyperpolarizing factor. Pflugers Arch. 2010;459:915–922.
  • Ellinsworth DC, Sandow SL, Shukla N, et al. Endothelium-derived hyperpolarization and coronary vasodilation: diverse and integrated roles of epoxyeicosatrienoic acides, hydrogen peroxide, and gap junctions. Microcirculation. 2015;23:15–32.
  • Sandow SL, Grayson TH. Limits of isolation and culture: intact vascular endothelium and BKCa. Am J Physiol Heart Circ Physiol. 2009;297:H1H9.
  • Gimbrone MA, Garcia CG. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res. 2016;118:620–636.
  • De Meyer GR, Herman AG. Vascular endothelial dysfunction. Prog Cardiovasc Dis. 1997;34:325–342.
  • Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000;87:840–844.
  • Cohen RA, Tong X. Vascular oxidative stress: The common link in hypertensive and diabetic vascular disease. J Cardiovasc Pharmacol. 2010;55:308–316.
  • Förstermann U. Nitric oxide and oxidative stress in vascular disease. Pflugers Arch. 2010;459:923–939.
  • Montezano AC, Dulak-Lis M, Tsiropoulou S, et al. Oxidative stress and human hypertension: Vascular mechanisms, biomarkers, and novel therapies. Can J Cardiol. 2015;31:631–641.
  • Ignarro LJ, Cirino G, Casini A, et al. Nitric oxide as a signaling molecule in the vascular system: an overview. J Cardiovasc Pharmacol. 1999;34:879–886.
  • Calles-Escandon J, Cipolla M. Diabetes and endothelial dysfunction: a clinical perspective. Endocrine Rev. 2001;22:36–52.
  • Creager MA, Lüscher TF, Cosentino F, et al. Diabetes and vascular disease. Pathophysiology, clinical consequences and medical therapy: part I. Circ. 2003;108:1527–1532.
  • De Vriese AS, Verbeuren TJ, Van de Voorde J, et al. Endothelial dysfunction in diabetes. Br J Pharmacol. 2000;130:963–974.
  • Potenza MA, Gagliardi S, Nacci C, et al. Endothelial dysfunction in diabetes: from mechanisms to therapeutic targets. Curr Med Chem. 2009;16:94–112.
  • Singh R, Barden A, Mori T, et al. Advanced glycation end-products: a review. Diabetologia. 2001;44:129–146.
  • Goldin A, Beckman JA, Schmidt AM, et al. Advanced glycation end products. Sparking the development of diabetic vascular injury. Circ. 2006;114:597–605.
  • Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–820.
  • Beckman JA, Paneni F, Cosentino F, et al. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part II. Eur Heart J. 2013;34:2444–2456.
  • Shimokawa H. Primary endothelial dysfunction: atherosclerosis. J Mol Cell Cardiol. 1999;31:23–37.
  • Paneni F, Beckman JA, Creager MA, et al. Diabetes and vascular disease: pathophysiology, clinical consequences and medical therapy: part I. Eur Heart J. 2013;34:2436–2446.
  • Gates PE, Strain WD, Shore AC. Human endothelial function and microvascular ageing. Exp Physiol. 2009;94:311–316.
  • Muller-Delp JM, Gurovich AN, Christou DD, et al. Redox balance in the aging microcirculation: New friends, new foes, and new clinical directions. Microcirculation. 2012;19:19–28.
  • Baschschmid MM, Schildknecht S, Matsui R, et al. Vascular aging: chronic oxidative stress and impairment of redox signaling-consequences for vascular homeostasis and disease. Ann Med. 2013;45:17–36.
  • Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res. 2015;116:1509–1526.
  • Donato AJ, Morgan RG, Walker AE, et al. Cellular and molecular biology of aging endothelial cells. J Mol Cell Cardiol. 2015;89:122–135.
  • Gutterman DD, Chabowski DS, Kadlec AO, et al. The human microcirculation: regulation of flow and Beyond Circ Res. 2016;118:157–172.
  • Bagher P, Segal SS. Regulation of blood flow in the microcirculation: role of conducted vasodilation. Acta Physiol (Oxf). 2011;202:271–284.
  • Behringer EJ, Shaw RL, Westcott EB, et al. Aging impairs electrical conduction along endothelium of resistance arteries through enhanced Ca2+-activated K+ channel activation. Artherioscler Thromb Vasc Biol. 2013;33:1892–1901.
  • Socha MJ, Boerman EM, Behringer EJ, et al. Advanced age protects microvascular endothelium from aberrant Ca2+ influx and cell death induced by hydrogen peroxide. J Physiol. 2015;593:2155–2169.
  • Boerman EM, Everhart JE, Segal SS. Advanced age decreased local calcium signaling in endothelium of mouse mesenteric arteries in vivo. Am J Physiol Heart Circ Physiol. 2016;310:H1091–H1096.
  • Félétou M, Vanhoutte PM. Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am J Physiol Heart Circ Physiol. 2006;291:H985–H1002.
  • Koltsova EK, Ley K. How dendritic cells shape atherosclerosis. Trends Immunol. 2011;32:540–547.
  • Tuttolomondo A, Di Raimondo D, Pecoraro R, et al. Atherosclerosis as an inflammatory disease. Curr Pharm Des. 2012;18:4266–4288.
  • Schulz C, Massberg S. Platelets in atherosclerosis and thrombosis. Handb Exp Pharmacol. 2012;210:111–133.
  • Bogdan C. Nitric oxide synthase in innate and adaptive immunity: an update. Trends Immunol. 2015;36:161–178.
  • Wolllard KJ. Immunological aspects of atherosclerosis. Clin Sci. 2013;125:221–235.
  • Pober JS, Sessa WC. Evolving functions of endothelial cells in inflammation. Nat Rev Immunol. 2007;7:803–815.
  • Danese S, Dejana E, Fiocchi C. Immune regulation by microvascular endothelial cells: directing innate and adaptive immunity, coagulation, and inflammation. J Immunol. 2007;178:6017–6022.
  • Witztum JL, Lichtman AH. The influence of innate and adaptive immune responses on atherosclerosis. Annu Rev Pathol Mech Dis. 2014;9:73–102.
  • Mann DL. The emerging role of innate immunity in the heart and vascular system: for whom the cell tolls. Circ Res. 2011;108:1133–1145.
  • Stokes KY. Microvascular responses to hypercholesterolemia: the interactions between innate and adaptive immune responses. Antioxidants and Redox Signaling. 2006;8:1141–1151.
  • Di Marco E, Gray SP, Jandeleit-Dahm K. Diabetes alters activation and repression of pro- and anti-inflammatory signaling pathways in the vasculature. Front Endocrinol. 2013;4:68.
  • Mai J, Virtue A, Shen J, et al. An evolving new paradigm: endothelial cells - conditional innate immune cells. J Hematol Oncol. 2013;6:61.
  • Spirig R, Tsui J, Shaw S. The emergingn role of TLR and innate immunity in cardiovascular disease. Cardiol Res Pract. 2012;2012:1–12.
  • Busse R, Fleming I, Hecker M. Signal transduction in endothelium-dependent vasodilatation. Eur Heart J. 1993;14 (suppl.1):2–9.
  • Ley K, Laudanna C, Cybulsky MI, et al. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007;7:678–689.
  • Morawietz H. LOX-1 and atherosclerosis: proof of concept in LOX-1-knockout mice. Circ Res. 2007;100:1534–1536.
  • Chaplin DD. Overview of the immune response. J Allergy Clin Immunol. 2010;125:S3–S23.
  • McEver RP. Selectins: initiators of leucocyte adhesion and signalling at the vascular wall. Cardiovasc Res. 2015;107:331–339.
  • Ley K, Miller YI, Hedrick CC. Monocyte and macrophage dynamics during atherogenesis. Arterioscler Thromb Vasc Biol. 2011;31:1506–1516.
  • Berezin A, Zulli A, Kerrigan S, et al. Predictive role of circulating endothelial-derived microparticles in cardiovascular diseases. Clin Biochem. 2015;48:562–568.
  • Jansen F, Nickenig G, Werner N. Extracellular vesicles in cardiovascular disease. Potential applications in diagnosis, prognosis and epidemiology. Circ Res. 2017;120:1649–1657.
  • Koga H, Sugiyama S, Kugiyama K, et al. Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease. J Am Coll Cardiol. 2005;45:1622–1630.
  • Sabatier F, Darmon P, Hugel B, et al. Type 1 and Type 2 diabetic patients display different patterns of cellular microparticles. Diabetes. 2002;51:2840–2845.
  • Gyorgy B, Szabo TG, Pasztoi M, et al. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci. 2011;68:2667–2688.
  • Martinez MC, Andriantsitohaina R. Extracellular vesicles in metabolic syndrome. Circ Res. 2017;120:1674–1686.
  • Lovren F, Verma S. Evolving role of microparticles in the pathophysiology of endothelial dysfunction. Clin Chem. 2013;59:1166–1174.
  • Schiro A, Wilkinson FL, Weston R, et al. Endothelial microparticles as conveyors of information in atherosclerotic disease. Atherosclerosis. 2014;234:295–302.
  • Boulanger C, Loyer X, Rautou PE, et al. Extracellular vesicles in coronary artery disease. Nat Rev Cardiol. 2017;14:259–272.
  • Triggle CR, Ding H. Endothelial dysfunction in diabetes: multiple targets for treatment. Pflugers Arch. 2010;459:977–994.
  • Anderson TJ, Charbonneau F, Title LM, et al. Microvascular function predicts cardiovascular events in primary prevention. Long-term results from the firefighters and their endothelium (FATE) study. Circ. 2011;123:163–169.
  • Hadi HAR, Al Suwaidi J. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag. 2007;3:853–876.
  • Tang EH, Vanhoutte PM. Endothelial dysfunction: a strategic target in the treatment of hypertension? Pflügers. Pflugers Arch. 2010;459:995–1004.
  • Tousoulis D, Papageorgiou N, Androulakis E, et al. Diabetes mellitus-associated vascular impairment: novel circulating biomarkers and therapeutic approaches. J Am Coll Cardiol. 2013;62:667–676.
  • Loscalzo J, Welch G. Nitric oxide and its role in the cardiovascular system. Prog Cardiovasc Dis. 1995;38:87–104.
  • Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA. 1991;88:4651–4655.
  • Furchgott RF. The role of endothelium in the responses of vascular smooth muscle to drugs. Annu Rev Pharmacol Toxicol. 1984;24:175–197.
  • Rhaleb NE, Yang XP, Carretero OA. The kallikrein-kinin system as a regulator of cardiovascular and renal function. Compr Physiol. 2011;1:971–993.
  • Oeseburg H, Iusuf D, van der Harst P, et al. Bradykinin protects aginst oxidative stress-induced endothelial cell senescence. Hypertension. 2009;53:417–422.
  • Mitchell JA, Ali F, Bailey L, et al. Role of nitric oxide and prostacyclin as vasoactive hormones released by the endothelium. Exp Physiol. 2007;93:141–147.
  • Blanco-Rivero J, Cachofeiro V, Lahera V, et al. Participation of prostacyclin in endothelial dysfunction induced by aldosterone in normotensive and hypertensive rats. Hypertension. 2005;46:107–112.
  • Félétou M, Huang Y, Vanhoutte PM. Endothelium-mediated control of vascular tone: COX-1 and COX-2 products. Br J Pharmacol. 2011;164:894–912.
  • Behrendt D, Ganz P. Endothelial function. From vascular biology to clinical applications. Am J Cardiol. 2002;90:40L–48L.
  • Spiecker M, Liao JK. Vascular protective effects of cytochrome p450 epoxygenase-derived eicosanoids. Arch Biochem Biophys. 2005;433:413–420.
  • Thorin E, Webb DJ. Endothelium-derived endothelin-1. Pflugers Arch. 2010;459:951–958.
  • Javeshghani D, Barhoumi T, Idris-Khodja N, et al. Reduced macrophage-dependent inflammation improves endothelin-1-induced vascular injury. Hypertension. 2013;62:112–117.

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