Skip to main content
SpringerLink
Log in

Signaling in the Endothelium

  • Chapter
  • First Online:
Signaling in the Heart

  • 1095 Accesses

Abstract

The endothelium regulates the tone of vascular smooth muscle cells at rest and during exercise, and the thrombotic and adhesive properties of the vascular wall. Endothelial cells are also responsible for vessel growth (angiogenesis) and inhibition of the positive inotropic and chronotropic responses of catecholamines in cardiomyocytes. Regulation occurs by releasing of relaxing factors and among them nitric oxide is the most important modulator of myocardial function. A comprehensive analysis of the ­signaling pathways network that regulates endothelium structure and function will be presented in this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Schwarz P, Diem R, Dun NJ, Forstermann U. Endogenous and exogenous nitric oxide inhibits norepinephrine release from rat heart sympathetic nerves. Circ Res. 1995;77:841–8.

    PubMed  CAS  Google Scholar 

  2. Kaye DM, Wiviott SD, Balligand J-L, Smith TW. Nitric oxide inhibits norepinephrine uptake into cardiac sympathetic neurons. Circulation. 1995;92 Suppl 1:I. Abstract.

    Google Scholar 

  3. Okhotin VE, Shuklin AV. Significance of neuronal, endothelial and inducible NO-synthase isoforms in the cardiac muscle histophysiology. Morfologiia. 2006;129(1):7–17.

    PubMed  CAS  Google Scholar 

  4. Fleming I, Fisslthaler B, Dimmeler S, Kemp BE, Busse R. Phosphorylation of Thr495 regulates Ca2+/calmodulin-dependent endothelial nitric oxide synthase activity. Circ Res. 2001;88:E68–75.

    PubMed  CAS  Google Scholar 

  5. Ladage D, Brixius K, Hoyer H, Steingen C, Wesseling A, Malan D, et al. Mechanisms underlying nebivolol-induced endothelial nitric oxide synthase activation in human umbilical vein endothelial cells. Clin Exp Pharmacol Physiol. 2006;33:720–4.

    PubMed  CAS  Google Scholar 

  6. Brouet A, Sonveaux P, Dessy C, Balligand JL, Feron O. Hsp90 ensures the transition from the early Ca2+-dependent to the late phosphorylation-dependent activation of the endothelial nitric-oxide synthase in vascular endothelial growth factor-exposed endothelial cells. J Biol Chem. 2001;276:32663–9.

    PubMed  CAS  Google Scholar 

  7. Zhong JC, Yu XY, Huang Y, Yung LM, Lau CW, Lin SG. Apelin modulates aortic vascular tone via endothelial nitric oxide synthase phosphorylation pathway in diabetic mice. Cardiovasc Res. 2007;74:388–95.

    PubMed  CAS  Google Scholar 

  8. Michell BJ, Harris MB, Chen ZP, Ju H, Venema VJ, Blackstone MA, et al. Identification of regulatory sites of phosphorylation of the bovine endothelial nitric-oxide synthase at serine 617 and serine 635. J Biol Chem. 2002;277:42344–51.

    PubMed  CAS  Google Scholar 

  9. Bauer PM, Fulton D, Boo YC, Sorescu GP, Kemp BE, Jo H, et al. Compensatory phosphorylation and protein–protein interactions revealed by loss of function and gain of function mutants of multiple serine phosphorylation sites in endothelial nitric oxide synthase. J Biol Chem. 2003;278:14841–9.

    PubMed  CAS  Google Scholar 

  10. Kou R, Greif D, Michel T. Dephosphorylation of endothelial nitric-oxide synthase by vascular endothelial growth factor. Implications for the vascular responses to cyclosporin A. J Biol Chem. 2002;277:29669–73.

    PubMed  CAS  Google Scholar 

  11. Erwin PA, Lin AJ, Golan DE, Michel T. Receptor-regulated dynamic S-nitrosylation of endothelial nitric-oxide synthase in vascular endothelial cells. J Biol Chem. 2005;280:19888–94.

    PubMed  CAS  Google Scholar 

  12. Feron O, Balligand J-L. Caveolins and the regulation of endothelial nitric oxide synthase in the heart. Cardiovasc Res. 2006;69:788–97.

    PubMed  CAS  Google Scholar 

  13. Icking A, Matt S, Opitz N, Wiesenthal A, Müller-Esterl W, Schilling K. NOSTRIN functions as a homotrimeric adaptor protein facilitating internalization of eNOS. J Cell Sci. 2005;118:5059–69.

    PubMed  CAS  Google Scholar 

  14. Sanchez FA, Savalia NB, Duran RG, Lal BK, Boric MP, Duran WN. Functional significance of differential eNOS translocation. Am J Physiol Heart Circ Physiol. 2006;291:H1058–64.

    PubMed  CAS  Google Scholar 

  15. Jagnandan D, Sessa WC, Fulton D. Intracellular location regulates calcium–calmodulin-dependent activation of organelle-restricted eNOS. Am J Physiol Cell Physiol. 2005;289:C1024–33.

    PubMed  CAS  Google Scholar 

  16. Church JE, Fulton D. Differences in eNOS activity because of subcellular localization are dictated by phosphorylation state rather than the local calcium environment. J Biol Chem. 2006;281:1477–88.

    PubMed  CAS  Google Scholar 

  17. Zhang Q, Church JE, Jagnandan D, Catravas JD, Sessa WC, Fulton D. Functional relevance of Golgi- and plasma membrane-localized endothelial NO synthase in reconstituted endothelial cells. Arterioscler Thromb Vasc Biol. 2006;26:1015–21.

    PubMed  CAS  Google Scholar 

  18. Erwin PA, Mitchell DA, Sartoretto J, Marletta MA, Michel T. Subcellular targeting and differential S-nitrosylation of endothelial nitric-oxide synthase. J Biol Chem. 2006;281:151–7.

    PubMed  CAS  Google Scholar 

  19. Jobin CM, Chen H, Lin AJ, Yacono PW, Igarashi J, Michel T, et al. Receptor-regulated dynamic interaction between endothelial nitric oxide synthase and calmodulin revealed by fluorescence resonance energy transfer in living cells. Biochemistry. 2003;42:11716–25.

    PubMed  CAS  Google Scholar 

  20. Tirziu D, Simons M. Endothelium-driven myocardial growth or nitric oxide at the crossroads. Trends Cardiovasc Med. 2008;18:299–305.

    PubMed  CAS  Google Scholar 

  21. Gonzalez DR, Treuer A, Sun QA, Stamler JS, Hare JM. S-nitrosylation of cardiac ion channels. J Cardiovasc Pharmacol. 2009;54(3):188–95.

    PubMed  CAS  Google Scholar 

  22. Hu RG, Sheng J, Qi X, et al. The N-end rule pathway as a nitric oxide sensor controlling the levels of multiple regulators. Nature. 2005;437:981–6.

    PubMed  CAS  Google Scholar 

  23. Sayed N, Baskaran P, Ma X, van den Akker F, Beuve A. Desensitization of soluble guanylyl cyclase, the NO receptor, by S-nitrosylation. Proc Natl Acad Sci USA. 2007;104:12312–7.

    PubMed  CAS  Google Scholar 

  24. McVey M, Hill J, Howlett A, Klein C. Adenylyl cyclase, a coincidence detector for nitric oxide. J Biol Chem. 1999;274:18887–92.

    PubMed  CAS  Google Scholar 

  25. Vila-Petroff MG, Younes A, Egan J, et al. Activation of distinct cAMP-dependent and cGMP-dependent pathways by nitric oxide in cardiac myocytes. Circ Res. 1999;84:1020–31.

    PubMed  CAS  Google Scholar 

  26. Fiedler B, Lohmann SM, Smolenski A, Linnemuller AS, Pieske B, Schroder F, et al. Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP-dependent protein kinase type I in cardiac myocytes. Proc Natl Acad Sci USA. 2002;99:11363–8.

    PubMed  CAS  Google Scholar 

  27. Heineke J, Kempf T, Kraft T, et al. Downregulation of cytoskeletal muscle LIM protein by nitric oxide: impact on cardiac myocyte hypertrophy. Circulation. 2003;107:1424–32.

    PubMed  CAS  Google Scholar 

  28. Cheng TH, Shih NL, Chen SY, et al. Nitric oxide inhibits ­endothelin-1-induced cardiomyocyte hypertrophy through cGMP mediated suppression of extracellular-signal regulated kinase phosphorylation. Mol Pharmacol. 2005;68:1183–92.

    PubMed  CAS  Google Scholar 

  29. Ozaki M, Kawashima S, Yamashita T, et al. Overexpression of endothelial nitric oxide synthase attenuates cardiac hypertrophy induced by chronic isoproterenol infusion. Circ J. 2002;66:851–6.

    PubMed  CAS  Google Scholar 

  30. Tirziu D, Chorianopoulos E, Moodie KL, Palac RT, Zhuang ZW, Tjwa M, et al. Myocardial hypertrophy in the absence of external stimuli is induced by angiogenesis in mice. J Clin Invest. 2007;117:3188–97.

    PubMed  CAS  Google Scholar 

  31. Huang PL, Huang Z, Mashimo H, Bloch KD, Moskowitz MA, Bevan JA, et al. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature. 1995;377:239–42.

    PubMed  CAS  Google Scholar 

  32. Chataigneau T, Félétou M, Huang PL, Fishman MC, Duhault J, Vanhoutte PM. Acetylcholine-induced relaxation in blood vessels from endothelial nitric oxide synthase knockout mice. Br J Pharmacol. 1999;126:219–26.

    PubMed  CAS  Google Scholar 

  33. Jansen-Olesen I, Ottosson A, Cantera L, Strunk S, Lassen LH, Olesen J, et al. Role of endothelium and nitric oxide in histamine-induced responses in human cranial arteries and detection of mRNA encoding H1- and H2-receptors by RT-PCR. Br J Pharmacol. 1997;121:41–8.

    PubMed  CAS  Google Scholar 

  34. De Nucci G, Thomas R, D’Orléans-Juste P, Antunes E, Walder C, Warner TD, et al. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci USA. 1988;85:9797–800.

    PubMed  Google Scholar 

  35. Tirapelli CR, Casolari DA, Yogi A, Monte-zano AC, Tostes RC, Legros E, et al. Functional characterization and expression of endothelin receptors in rat carotid artery: involvement of nitric oxide, a vasodilator prostanoid and the opening of K+ channels in ET B-induced relaxation. Br J Pharmacol. 2005;146:903–12.

    PubMed  CAS  Google Scholar 

  36. Sakata K, Ozaki H, Kwon SC, Karaki H. Effects of endothelin on the mechanical activity and cytosolic calcium level of various types of smooth muscle. Br J Pharmacol. 1989;98:483–92.

    PubMed  CAS  Google Scholar 

  37. Tirapelli CR, Bonaventura D, Tirapelli LF, de Oliveira AM. Mechanisms underlying the vascular actions of endothelin 1, angiotensin II and bradykinin in the rat carotid. Pharmacology. 2009;84:111–26.

    PubMed  CAS  Google Scholar 

  38. Friebe A, Mergia E, Dangel O, Lange A, Koesling D. Fatal gastrointestinal obstruction and hypertension in mice lacking nitric oxide-sensitive guanylyl cyclase. Proc Natl Acad Sci USA. 2007;104:7699–704.

    PubMed  CAS  Google Scholar 

  39. Pfeifer A, Klatt P, Massberg S, Ny L, Sausbier M, Hirneiss C, et al. Defective smooth muscle regulation in cGMP kinase I-deficient mice. EMBO J. 1998;17:3045–51.

    PubMed  CAS  Google Scholar 

  40. Papapetropoulos A, Garcia-Cardena G, Madri JA, Sessa WC. Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest. 1997;100:3131–9.

    PubMed  CAS  Google Scholar 

  41. Amano K, Matsubara H, Iba O, et al. Enhancement of ischemia-induced angiogenesis by eNOS overexpression. Hypertension. 2003;41:156–62.

    PubMed  CAS  Google Scholar 

  42. Simons M. Molecular multitasking: statins lead to more arteries, less plaque. Nat Med. 2000;6:965–6.

    PubMed  CAS  Google Scholar 

  43. Brouet A, Sonveaux P, Dessy C, Moniotte S, Balligand J-L, Feron O. Hsp90 and caveolin are key targets for the proangiogenic nitric oxide-mediated effects of statins. Circ Res. 2001;89:866–73.

    PubMed  CAS  Google Scholar 

  44. Sonveaux P, Martinive P, DeWever J, Batova Z, Daneau G, Pelat M, et al. Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic Hindlimb collateralization and nitric oxide-mediated angiogenesis. Circ Res. 2004;95:154–61.

    PubMed  CAS  Google Scholar 

  45. Wise H, Jones RL. Focus on prostacyclin and its novel mimetics. Trends Pharmacol Sci. 1996;17:17–21.

    PubMed  CAS  Google Scholar 

  46. Gluais P, Lonchampt M, Morrow JD, Vanhoutte PM, Feletou M. Acetylcholine-induced endothelium-dependent contractions in the SHR aorta: the Janus face of prostacyclin. Br J Pharmacol. 2005;146:834–45.

    PubMed  CAS  Google Scholar 

  47. Barrow SE, Dollery CT, Heavey DJ, Hickling NE, Ritter JM, Vial J. Effect of vasoactive peptides on prostacyclin synthesis in man. Br J Pharmacol. 1986;87:243–7.

    PubMed  CAS  Google Scholar 

  48. Tang EH, Ku DD, Tipoe GL, Feletou M, Man RY, Vanhoutte PM. Endothelium-dependent contractions occur in the aorta of wildtype and COX2−/− knockout but not COX1−/− knockout mice. J Cardiovasc Pharmacol. 2005;46:761–5.

    PubMed  CAS  Google Scholar 

  49. Heymes C, Habib A, Yang D, Mathieu E, Marotte F, Samuel J-L, et al. Cyclo-oxygenase-1 and -2 contribution to endothelial dysfunction in ageing. Br J Pharmacol. 2000;131:804–10.

    PubMed  CAS  Google Scholar 

  50. Vanhoutte PM, Feletou M, Taddei S. Endothelium-dependent contractions in hypertension. Br J Pharmacol. 2005;144:449–58.

    PubMed  CAS  Google Scholar 

  51. Wilson DP, Susnjar M, Kiss E, Sutherland C, Walsh MP. Thromboxane A2-induced contraction of rat caudal arterial smooth muscle involves activation of Ca2+ entry and Ca2+ sensitization: rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697. Biochem J. 2005;389:763–74.

    PubMed  CAS  Google Scholar 

  52. Gluais P, Vanhoutte PM, Feletou M. Mechanisms underlying ATP-induced endothelium-dependent contractions in the SHR aorta. Eur J Pharmacol. 2007;556:107–14.

    PubMed  CAS  Google Scholar 

  53. Dominiczak AF, Quilley J, Bohr DF. Contraction and relaxation of rat aorta in response to ATP. Am J Physiol. 1991;261:H243–51.

    PubMed  CAS  Google Scholar 

  54. Bund SJ. Influence of mode of contraction on the mechanism of acetylcholine-mediated relaxation of coronary arteries from normotensive and spontaneously hypertensive rats. Clin Sci (Lond). 1998;94:231–8.

    CAS  Google Scholar 

  55. Muller L, Barret A, Etienne E, Meidan R, Valdenaire O, Corvol P, et al. Heterodimerization of endothelin-converting enzyme-1 isoforms regulates the subcellular distribution of this metalloprotease. J Biol Chem. 2003;278:545–55.

    PubMed  CAS  Google Scholar 

  56. Zhou J, Zhu Y, Cheng M, Dinesh D, Thorne T, Poh KK, et al. Regulation of vascular contractility and blood pressure by the E2F2 transcription factor. Circulation. 2009;120:1213–21.

    PubMed  CAS  Google Scholar 

  57. Funke-Kaiser H, Reichenberger F, Kopke K, Herrmann SM, Pfeifer J, Orzechowski HD, et al. Differential binding of transcription factor E2F-2 to the endothelin-converting enzyme-1b promoter affects blood pressure regulation. Hum Mol Genet. 2003;12:423–33.

    PubMed  CAS  Google Scholar 

  58. Funalot B, Courbon D, Brousseau T, Poirier O, Berr C, Cambien F, et al. Genes encoding endothelin-converting enzyme-1 and endothelin-1 interact to influence blood pressure in women: the EVA study. J Hypertens. 2004;22:739–43.

    PubMed  CAS  Google Scholar 

  59. Dammanahalli JK, Sun Z. Endothelin (ET)-1 inhibits nicotinamide adenine dinucleotide phosphate oxidase activity in human abdominal aortic endothelial cells: a novel function of ETB1 receptors. Endocrinology. 2008;149:4979–87.

    PubMed  CAS  Google Scholar 

  60. Calo G, Gratton JP, Telemaque S, D’Orleans-Juste P, Regoli D. Pharmacology of endothelins: vascular preparations for studying ETA and ETB receptors. Mol Cell Biochem. 1996;154:31–7.

    PubMed  CAS  Google Scholar 

  61. Verhaar MC, Strachan FE, Newby DE, Cruden NL, Koomans HA, Rabelink TJ, et al. Endothelin-A receptor antagonist-mediated vasodilatation is attenuated by inhibition of nitric oxide synthesis and by endothelin-B receptor blockade. Circulation. 1998;97:752–6.

    PubMed  CAS  Google Scholar 

  62. Hollenberg NK, Fisher NDL, Price DA. Pathways for angiotensin II generation in intact human tissue: evidence from comparative pharmacological interruption of the renin system. Hypertension. 1998;32:387–92.

    PubMed  CAS  Google Scholar 

  63. Becari C, Sivieri Jr DO, Santos CF, Moyses MK, Oliveira EB, Salgado MC. Role of elastase-2 as an angiotensin II-forming enzyme in rat carotid artery. J Cardiovasc Pharmacol. 2005;46:498–504.

    PubMed  CAS  Google Scholar 

  64. Santos CF, Caprio MA, Oliveira EB, Salgado MC, Schippers DN, Munzenmaier DH, et al. Functional role, cellular source, and tissue distribution of rat elastase-2, an angiotensin II-forming enzyme. Am J Physiol Heart Circ Physiol. 2003;285:H775–83.

    PubMed  CAS  Google Scholar 

  65. Fukada SY, Iyomasa MM, Cunha FQ, Correa FM, de Oliveira AM. Mechanisms of impaired vascular response to Ang II in perivascular injured carotid arteries of ovariectomized rat. J Cardiovasc Pharmacol. 2004;44:393–400.

    PubMed  CAS  Google Scholar 

  66. Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol. 2007;292:C82–97.

    PubMed  CAS  Google Scholar 

  67. Santos RAS, Simões e Silva AC, Maric C, Silva DMR, Machado RP, Buhr I, et al. Angiotensin-(1–7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci USA. 2003;100:8258–63.

    PubMed  CAS  Google Scholar 

  68. Igase M, Strawn WB, Gallagher PE, Geary RL, Ferrario CM. Angiotensin II AT 1 receptors regulate ACE2 and angiotensin-(1–7) expression in the aorta of spontaneously hypertensive rats. Am J Physiol. 2005;289:H1013–9.

    CAS  Google Scholar 

  69. Fukada SY, Tirapelli CR, de Godoy MA, de Oliveira AM. Mechanisms underlying the endothelium-independent relaxation induced by angiotensin II in rat aorta. J Cardiovasc Pharmacol. 2005;45:136–43.

    PubMed  CAS  Google Scholar 

  70. Castro-Chaves P, Soares S, Fontes-Carvalho R, Leite-Moreira AF. Negative inotropic effect of selective AT2 receptor stimulation and its modulation by the endocardial endothelium. Eur J Pharmacol. 2008;578:261–9.

    PubMed  CAS  Google Scholar 

  71. Yayama K, Okamoto H. Angiotensin II-induced vasodilation via type 2 receptor: role of bradykinin and nitric oxide. Int Immunopharmacol. 2008;8:312–8.

    PubMed  CAS  Google Scholar 

  72. Wassmann S, Nickenig G. Pathophysiological regulation of the AT1-receptor and implications for vascular disease. J Hypertens. 2006;24 Suppl 1:S15–21.

    CAS  Google Scholar 

  73. Bhoola KD, Figueroa CD, Worthy K. Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev. 1992;44:1–80.

    PubMed  CAS  Google Scholar 

  74. Michel T, Li GK, Busconi L. Phosphorylation and subcellular translocation of endothelial nitric oxide synthase. Proc Natl Acad Sci USA. 1993;90:6252–6.

    PubMed  CAS  Google Scholar 

  75. Barrow SE, Dollery CT, Heavey DJ, Hickling NE, Ritter JM, Mial J. Effect of vasoactive peptides on prostacyclin synthesis in man. Br J Pharmacol. 1986;87:243–7.

    PubMed  CAS  Google Scholar 

  76. Tsutsumi Y, Matsubara H, Masaki H, Kurihara H, Murasawa S, Takai S, et al. Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation. J Clin Invest. 1999;104:925–35.

    PubMed  CAS  Google Scholar 

  77. Batenburg WW, Garrelds IM, Bernasconi CC, Juillerat-Jeanneret L, van Kats JP, Saxena PR, et al. Angiotensin II type 2 receptor-mediated vasodilation in human coronary microarteries. Circulation. 2004;109:2296–301.

    PubMed  CAS  Google Scholar 

  78. Busse R, Lamontagne D. Endothelium-derived bradykinin is responsible for the increase in calcium produced by angiotensin-converting enzyme inhibitors in human endothelial cells. Naunyn Schrniedebergs Arch Pharmacol. 1991;344:126–9.

    CAS  Google Scholar 

  79. Landmesser U, Drexler H. Effect of angiotensin II type 1 receptor antagonism on endothelial function: role of bradykinin and nitric oxide. J Hypertens. 2006;24 Suppl 1:S39–43.

    CAS  Google Scholar 

  80. Zafari AM, Ushio-Fukai M, Akers M, Yin Q, Shah A, Harrison DG, et al. Novel role of NADH/NADPH oxidase-derived hydrogen peroxide in angiotensin II-induced hypertrophy of rat vascular smooth muscle cells. Hypertension. 1998;32:488–95.

    PubMed  CAS  Google Scholar 

  81. Irani K, Xia Y, Zweier JL, Sollott SJ, Der CJ, Fearon ER, et al. Mitogenic signaling mediated by oxidants in ras-transformed fibroblasts. Science. 1997;275:1649–52.

    PubMed  CAS  Google Scholar 

  82. Marumo T, Schini-Kerth VB, Fisslthaler B, Busse R. Platelet-derived growth factor-stimulated superoxide anion production modulates activation of transcription factor NF-κB and expression of monocyte chemoattractant protein-1 in human aortic smooth muscle cells. Circulation. 1997;96:2361–7.

    PubMed  CAS  Google Scholar 

  83. Patterson C, Ruef J, Madamanchi NR, Barry-Lane P, Hu Z, Horaist C, et al. Stimulation of a vascular smooth muscle cell NAD(P)H oxidase by thrombin: evidence that p47(phox) may participate in forming this oxidase in vitro and in vivo. J Biol Chem. 1999;274:19814–22.

    PubMed  CAS  Google Scholar 

  84. De Keulenaer GW, Alexander RW, Ushio-Fukai M, Ishizaka N, Griendling KK. Tumor necrosis factor-α activates a p22phox-based NADH oxidase in vascular smooth muscle cells. Biochem J. 1998;329:653–7.

    PubMed  Google Scholar 

  85. Gorlach A, Brandes RP, Nguyen K, Amidi M, Dehghani F, Busse RA. gp91phox containing NADPH oxidase selectively expressed in endothelial cells is a major source of oxygen radical generation in the arterial wall. Circ Res. 2000;87:26–32.

    PubMed  CAS  Google Scholar 

  86. Suh Y, Arnold RS, Lassègue B, Shi J, Xu X, Sorescu D, et al. Cell transformation by the superoxide-generating oxidase mox1. Nature. 1999;401:79–82.

    PubMed  CAS  Google Scholar 

  87. Jones SA, O’Donnell VB, Wood JD, Broughton JP, Hughes EJ, Jones OTG. Expression of phagocyte NADPH oxidase components in human endothelial cells. Am J Physiol. 1996;271:H1626–34.

    PubMed  CAS  Google Scholar 

  88. Touyz RM, Schiffrin EL. Ang II-stimulated superoxide production is mediated via phospholipase D in human vascular smooth ­muscle cells. Hypertension. 1999;34:976–82.

    PubMed  CAS  Google Scholar 

  89. Seshiah PN, Weber DS, Rocic P, Valppu L, Taniyama Y, Griendling KK. Angiotensin II stimulation of NAD(P)H oxidase activity: upstream mediators. Circ Res. 2002;91:406–13.

    PubMed  CAS  Google Scholar 

  90. Gomez-Cambronero J, Keire P. Phospholipase D: a novel major player in signal transduction. Cell Signal. 1998;10:387–97.

    PubMed  CAS  Google Scholar 

  91. Paravicini TM, Touyz RM. Redox signaling in hypertension. Cardiovasc Res. 2006;71:247–58.

    PubMed  CAS  Google Scholar 

  92. de Bold AJ, Ma KK, Zhang Y, de Bold ML, Bensimon M, Khoshbaten A. The physiological and pathophysiological modulation of the endocrine function of the heart. Can J Physiol Pharmacol. 2001;79:705–14.

    PubMed  Google Scholar 

  93. Olney RC. C-type natriuretic peptide in growth: a new paradigm. Growth Horm IGF Res. 2006;16:S6–14.

    PubMed  CAS  Google Scholar 

  94. Kuhn M. Function and dysfunction of mammalian membrane guanylyl cyclase receptors: lessons from genetic mouse models and implications for human diseases. In: Schmidt HHHW et al., editors. cGMP: generators, effectors and therapeutic implications, Handbook of experimental pharmacology, vol. 191. Berlin: Springer; 2009. p. 47–69.

    Google Scholar 

  95. Holtwick R, Gotthardt M, Skryabin B, Steinmetz M, Potthast R, Zetsche B, et al. Smooth muscle-selective deletion of guanylyl cyclase-A prevents the acute but not chronic effects of ANP on blood pressure. Proc Natl Acad Sci USA. 2002;99:7142–7.

    PubMed  CAS  Google Scholar 

  96. Holtwick R, Van Eickels M, Skryabin BV, Baba HA, Bubikat A, Begrow F, et al. Pressure-independent cardiac hypertrophy in mice with cardiomyocyte-restricted inactivation of the atrial natriuretic peptide receptor guanylyl cyclase-A. J Clin Invest. 2003;111:1399–407.

    PubMed  CAS  Google Scholar 

  97. Sabrane K, Kruse MN, Fabritz L, Zetsche B, Mitko D, Skryabin BV, et al. Vascular endothelium is critically involved in the hypotensive and hypovolemic actions of atrial natriuretic peptide. J Clin Invest. 2005;115:1666–74.

    PubMed  CAS  Google Scholar 

  98. Tamura N, Ogawa Y, Chusho H, Nakamura K, Nakao K, Suda M, et al. Cardiac fibrosis in mice lacking brain natriuretic peptide. Proc Natl Acad Sci USA. 2000;97:4239–44.

    PubMed  CAS  Google Scholar 

  99. Kapoun AM, Liang F, O’Young G, Damm DL, Quon D, White RT, et al. B-type natriuretic peptide exerts broad functional opposition to transforming growth factor-beta in primary human cardiac fibroblasts: fibrosis, myofibroblast conversion, proliferation, and inflammation. Circ Res. 2004;94:453–61.

    PubMed  CAS  Google Scholar 

  100. Kemp-Harper B, Schmidt HHHW. cGMP in the Vasculature. In: Schmidt HHHW et al., editors. cGMP: generators, effectors and therapeutic implications, Handbook of experimental pharmacology, vol. 191. Berlin: Springer; 2009. p. 447–67.

    Google Scholar 

  101. Yamahara K, Itoh H, Chun TH, Ogawa Y, Yamashita J, Sawada N, et al. Significance and therapeutic potential of the natriuretic peptides/cGMP/cGMP-dependent protein kinase pathway in vascular regeneration. Proc Natl Acad Sci USA. 2003;100:3404–9.

    PubMed  CAS  Google Scholar 

  102. Komatsu Y, Ito H, Suga S, Ogawa Y, Hama N, Kishimoto I, et al. Regulation of endothelial production of C-type natriuretic peptide in coculture with vascular smooth muscle cells. Role of the vascular natriuretic peptide system in vascular growth inhibition. Circ Res. 1996;78:606–14.

    PubMed  CAS  Google Scholar 

  103. Pagel-Langenickel I, Buttgereit J, Bader M, Langenickel TH. Natriuretic peptide receptor B signaling in the cardiovascular system: protection from cardiac hypertrophy. J Mol Med. 2007;85:797–810.

    PubMed  CAS  Google Scholar 

  104. Meyer D, Birchmeier C. Multiple essential functions of neuregulin in development. Nature. 1995;378:386–90.

    PubMed  CAS  Google Scholar 

  105. Carraway III KL, Weber JL, Unger MJ, Ledesma J, Yu N, Gassmann M, et al. Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases. Nature. 1997;387:512–6.

    PubMed  CAS  Google Scholar 

  106. Baliga RR, Pimental DR, Zhao YY, Simmons WW, Marchionni MA, Sawyer DB, et al. NRG-1-induced cardiomyocyte hypertrophy. Role of PI-3-kinase, p70(S6K), and MEK-MAPKRSK. Am J Physiol. 1999;277:H2026–37.

    PubMed  CAS  Google Scholar 

  107. Zhao Y, Sawyer DR, Baliga RR, Opel DJ, Han X, Marchionni MA, et al. Neuregulins promote survival and growth of cardiac myocytes. Persistence of ErbB2 and ErbB4 expression in neonatal and adult ventricular myocytes. J Biol Chem. 1998;273:10261–9.

    PubMed  CAS  Google Scholar 

  108. Lemmens K, Segers VF, Demolder M, De Keulenaer GW. Role of neuregulin-1/ErbB2 signaling in endothelium-cardiomyocyte cross-talk. J Biol Chem. 2006;281:19469–77.

    PubMed  CAS  Google Scholar 

  109. Lemmens K, Fransen P, Sys SU, Brutsaert DL, De Keulenaer GW. Neuregulin-1 induces a negative inotropic effect in cardiac muscle: role of nitric oxide synthase. Circulation. 2004;109:324–6.

    PubMed  CAS  Google Scholar 

  110. Crone SA, Zhao YY, Fan L, Gu Y, Minamisawa S, Liu Y, et al. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med. 2002;8:459–65.

    PubMed  CAS  Google Scholar 

  111. Rohrbach S, Yan X, Weinberg EO, Hasan F, Bartunek J, Marchionni MA, et al. Neuregulin in cardiac hypertrophy in rats with aortic stenosis: differential expression of erbB2 and erbB4 receptors. Circulation. 1999;100:407–12.

    PubMed  CAS  Google Scholar 

  112. Lemmens K, Doggen K, De Keulenaer GW. Role of neuregulin-1/erbB signaling in cardiovascular physiology and disease. Implications for therapy of heart failure. Circulation. 2007;116:954–60.

    PubMed  CAS  Google Scholar 

  113. Liu X, Gu X, Li Z, Li X, Li H, Chang J, et al. Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy. J Am Coll Cardiol. 2006;48:1438–47.

    PubMed  CAS  Google Scholar 

  114. Caporali A, Emanueli C. Cardiovascular actions of neurotrophins. Physiol Rev. 2009;89:279–308.

    PubMed  CAS  Google Scholar 

  115. Shmelkov SV, Meeus S, Moussazadeh N, Kermani P, Rashbaum WK, Rabbany SY, et al. Cytokine preconditioning promotes codifferentiation of human fetal liver CD133+ stem cells into angiomyogenic tissue. Circulation. 2005;111:1175–83.

    PubMed  CAS  Google Scholar 

  116. Donovan MJ, Lin MI, Wiegn P, Ringstedt T, Kraemer R, Hahn R, et al. Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization. Development. 2000;127:4531–40.

    PubMed  CAS  Google Scholar 

  117. Wagner N, Wagner KD, Theres H, Englert C, Schedl A, Scholz H. Coronary vessel development requires activation of the TrkB neurotrophin receptor by the Wilms’ tumor transcription factor Wt1. Genes Dev. 2005;19:2631–42.

    PubMed  CAS  Google Scholar 

  118. Anfuso CD, Lupo G, Romeo L, Giurdanella G, Motta C, Pascale A, et al. Endothelial cell-pericyte cocultures induce PLA2 protein expression through activation of PKCα and the MAPK/ERK cascade. J Lipid Res. 2007;48:782–93.

    PubMed  CAS  Google Scholar 

  119. Chen KD, Li YS, Kim M, Li S, Yuan S, Chien S, et al. Mechanotransduction in response to shear stress. Roles of receptor tyrosine kinases, integrins, and Shc. J Biol Chem. 1999;274:18393–400.

    PubMed  CAS  Google Scholar 

  120. Li S, Chen BP, Azuma N, Hu YL, Wu SZ, Sumpio BE, et al. Distinct roles for the small GTPases Cdc42 and Rho in endothelial responses to shear stress. J Clin Invest. 1999;103:1141–50.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Molecular Cardiology and Neuromuscular Institute, Raritan Avenue 75, 08904, Highland Park, NJ, USA

    José Marín-García M.D. (Director)

Authors
  1. José Marín-García M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to José Marín-García M.D. .

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Marín-García, J. (2011). Signaling in the Endothelium. In: Signaling in the Heart. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9461-5_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-9461-5_3

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-9460-8

  • Online ISBN: 978-1-4419-9461-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation