Skip to main content
SpringerLink
Log in

Endocardial—Myocardial Interaction

  • Chapter
Cardiac-Vascular Remodeling and Functional Interaction

  • 99 Accesses

Summary

In 1986, Brutsaert et al. observed that the endocardial endothelium (EE) directly controls performance of the myocardium. From this observation, the existence of an endocardium-mediated intracavitary autoregulation of cardiac performance has been postulated. Recent discoveries on morphology and function of the endocardium have substantiated this hypothesis. Morphologically, phenotypic expression of several receptors, tight and gap junctions, adhesion molecules, intercellular clefts, and a specific organization of the cytoskeleton distinguishes the EE from other endothelial subtypes and emphasizes a structural and functional specialization. Functionally, the EE imparts a twitch-prolonging and positive inotropic effect on cardiac muscle, apparently by enhancing the responsiveness of myocardial contractile proteins to Ca2+. EE-mediated control of myocardial performance resembles length/volume-mediated control and interacts with neurohumoral-mediated control. EE cells respond to physical and humoral stimuli with release of several substances that have important inotropic actions on the myocardium. Specific electrophysiological properties determine the intracellular Ca2+ increase in response to external stimuli and modulate the release of these substances. An asymmetrical distribution of ion channels between the luminal and abluminal membrane of the EE suggests a specific transendothelial transport of ions over the endocardium. Accordingly, the endocardium is highly specialized for communication with and regulation of the myocardium. It will be interesting to evaluate endocardium-mediated control of cardiac performance in pathophysiological conditions.

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 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Furchgott RF, Zawadski JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288: 373–376

    Article  PubMed  CAS  Google Scholar 

  2. Brutsaert DL, Meulemans AL, Sipido KR, Sys SU (1988) Effects of damaging the endocardial surface on the mechanical performance of isolated cardiac muscle. Circ Res 62: 357–366

    Article  Google Scholar 

  3. De Hert SG, Gillebert TC, Brutsaert DL (1993) Alteration of left ventricular endocardial function by intracavitary high-power ultrasound interacts with volume, inotropic state, and alpha,-adrenergic stimulation. Circulation 87: 1275–1285

    Article  PubMed  Google Scholar 

  4. Gillebert TC, De Hert SG, Andries LJ, Jageneau AH, Brutsaert DL (1992) Intracavitary ultrasound impairs left ventricular performance: presumed role of endocardial endothelium. Am J Physiol 263: H857 - H865

    PubMed  CAS  Google Scholar 

  5. Brutsaert DL (1993) Endocardial and coronary endothelial control of cardiac performance. News Physiol Sci 8: 82–86

    Google Scholar 

  6. Brutsaert DL, Andries LJ (1992) The endocardial endothelium. Am J Physiol 263: H985 - H1002

    PubMed  CAS  Google Scholar 

  7. Wilcox JN, Augustine A, Goeddel DV, Lowe DG (1991) Differential regional expression of three natriuretic peptide receptor genes within primate tissues. Mol Cell Biol 11: 3454–3462

    PubMed  CAS  Google Scholar 

  8. Lombès M, Oblin ME, Gasc JM, Baulieu EE, Farman N, Bonvalet JP (1992) Immunohistochemical and biochemical evidence for a cardiovascular mineralocorticoid receptor. Circ Res 71: 503–510

    Article  PubMed  Google Scholar 

  9. Molenaar P, O’Reilly G, Sharkey A, Kuc RE, Harding DP, Plumpton C, Gresham GA, Davenport AP (1993) Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium. Circ Res 72: 526–538

    Article  PubMed  CAS  Google Scholar 

  10. Wharton J, Rutherford RA, Gordon L, Moscoso G, Schiemberg I, Gaer JA, Taylor KM, Polak JM (1991) Localization of endothelin binding sites and endothelinlike immunoreactivity in human fetal heart. J Cardiovasc Pharmacol 7 (suppl 17): S378 - S384

    Article  Google Scholar 

  11. Yamada H, Fabris B, Allen AM, Jackson B, Johnston CI, Mendelsohn AO (1991) Localization of angiotensin-converting enzyme in rat heart. Circ Res 68: 141–149

    Article  PubMed  CAS  Google Scholar 

  12. Page C, Rose M, Yacoub M, Pigott R (1992) Antigenic heterogeneity of vascular endothelium. Am J Pathol 141: 673–683

    PubMed  CAS  Google Scholar 

  13. Tanaka H, Sukhova GK, Swanson SJ, Cybulsky MI, Schoen FJ, Libby P (1994) Endothelial and smooth muscle cells express leukocyte adhesion molecules heterogeneously during acute rejection of rabbit cardiac allografts. Am J Pathol 144: 938–951

    PubMed  CAS  Google Scholar 

  14. Taylor PM, Rose ML, Yacoub MH, Pigott R (1992) Induction of vascular adhesion molecules during rejection of human cardiac allografts. Transplantation 54(3): 451457

    Google Scholar 

  15. Yamazaki T, Seko Y, Tamtani T, Myasaka M, Yagita H, Okumura K, Nagai R, Yazaki Y (1993) Expression of intercellular adhesion molecule-1 in rat heart with ischemia/ reperfusion and limitation of infarct size by treatment with antibodies against cell adhesion molecules. Am J Pathol 143: 410–418

    PubMed  CAS  Google Scholar 

  16. Andries LJ (1994) Endocardial endothelium: functional morphology. Landes, Austin, p 143

    Google Scholar 

  17. Andries LJ, Brutsaert DL (1991) Differences in functional structure between endocardial endothelium and vascular endothelium. J Cardiovasc Pharmacol 17 (suppl 3): S243 - S246

    Article  Google Scholar 

  18. Anversa P, Giacomelli F, Wiener J (1975) Intercellular junctions of rat endocardium. Anat Rec 183: 477–484

    Article  PubMed  CAS  Google Scholar 

  19. Rotrosen D, Gallin JI (1986) Histamine type I receptor occupancy increases endothelial cytosolic calcium, reduces F-actin, and promotes albumin diffusion across cultured endothelial monolayers. J Cell Biol 103: 2379–2387

    Article  PubMed  CAS  Google Scholar 

  20. Schnittler HJ, Wilke A, Gress T, Suttorp N, Drenckhahn D (1990) Role of actin and myosin in the control of paracellular permeability in pig, rat and human vascular endothelium. J Physiol (Camb) 431: 379–401

    CAS  Google Scholar 

  21. Wysolmerski RB, Lagunoff D (1988) Inhibition of endothelial cell retraction by ATP depletion. Am J Pathol 132: 28–37

    PubMed  CAS  Google Scholar 

  22. Gotlieb AI, Langille L, Wong MKK, Kim DW (1991) Biology of disease. Structure and function of the endothelial cytoskeleton. Lab Invest 65: 123–137

    Google Scholar 

  23. White GE, Gimbrone MA, Fujiwara K (1983) Factors influencing the expression of stress fibers in vascular endothelial cells in situ. J Cell Biol 97: 417–424

    Google Scholar 

  24. Andries LJ, Brutsaert DL (1993) Endocardial endothelium in rat heart: cell shape and organization of the cytoskeleton. Cell Tissue Res 273: 107–117

    Article  PubMed  CAS  Google Scholar 

  25. Dartsch PC, Betz E (1989) Response of cultured endothelial cells to mechanical stimulation. Basic Res Cardiol 84: 268–281

    Article  PubMed  CAS  Google Scholar 

  26. Iba T, Sumpio BE (1991) Morphological response of human endothelial cells subjected to cyclic strain in vitro. Microvasc Res 42: 245–254

    Article  PubMed  CAS  Google Scholar 

  27. Shirinsky VP, Antonov AS, Birukov KG, Sobolevsky AV, Romanov YA, Kabaeva NV, Antanova GN, Smirnov VN (1989) Mechano-chemical control of human endothelium orientation and size. J Cell Biol 109: 331–339

    Article  PubMed  CAS  Google Scholar 

  28. Andries LJ, Brutsaert DL (1994) Endocardial endothelium: junctional organization and permeability. Cell Tissue Res 277: 391–400

    Article  PubMed  CAS  Google Scholar 

  29. Melax H, Leeson TS (1967) Fine structure of the endocardium in adult rats. Cardiovasc Res 1: 349–355

    Article  PubMed  CAS  Google Scholar 

  30. Li K, Rouleau JL, Andries LJ, Brutsaert DL (1993) Effect of dysfunctional vascular endothelium on myocardial performance in isolated papillary muscles. Circ Res 72: 768–777

    Article  PubMed  CAS  Google Scholar 

  31. Li K, Rouleau JL, Calderone A, Andries LJ, Brutsaert DL (1993) Endocardial function in pacing-induced heart failure in the dog. J Mol Cell Cardiol 25: 529–538

    Article  PubMed  CAS  Google Scholar 

  32. Shah AM, Smith JA, Lewis MJ (1991) The role of endocardium in the modulation of contraction of isolated papillary muscles of the ferret. J Cardiovasc Pharmacol 17: S251 - S257

    Article  Google Scholar 

  33. Fort S, Lewis MJ, Shah AM (1993) The role of endocardial endothelium in the modulation of myocardial contraction in the isolated whole heart. Cardioscience 4: 217–222

    PubMed  CAS  Google Scholar 

  34. Wang J, Morgan JP (1992) Endocardial endothelium modulates myofilament Cat+ responsiveness in aequorin-loaded ferret myocardium. Circ Res 70: 754–760

    Article  PubMed  CAS  Google Scholar 

  35. Brutsaert DL, Sys SU (1989) Relaxation and diastole of the heart. Physiol Rev 69: 12281315

    Google Scholar 

  36. Meulemans AL, Sipido KR, Sys SU, Brutsaert DL (1988) Atriopeptin III induces early relaxation of isolated mammalian papillary muscle. Circ Res 62: 1171–1174

    Article  PubMed  CAS  Google Scholar 

  37. Meulemans AL, Andries LJ, Brutsaert DL (1990) Endocardial endothelium mediates positive inotropic response to alpha,-adrenoreceptor agonist in mammalian heart. J Mol Cell Cardiol 22: 667–685

    Article  PubMed  CAS  Google Scholar 

  38. De Keulenaer GW, Andries LJ, Sys SU, Brutsaert DL (1995) Endothelin-mediated positive inotropic effect by free radicals in isolated cardiac muscle. Circ Res 76: 878884

    Google Scholar 

  39. Shah AM, Andries LJ, Meulemans AL, Brutsaert DL (1989) Endocardium modulates inotropic response to 5-hydroxytryptamine. Am J Physiol 257: H1790 - H1797

    PubMed  CAS  Google Scholar 

  40. Schoemaker IE, Meulemans AL, Andries LJ, Brutsaert DL (1990) Role of the endocardial endothelium in the positive inotropic action of vasopressin. Am J Physiol 259: H1148 - H1151

    PubMed  CAS  Google Scholar 

  41. Mohan P, Brutsaert DL, Sys SU (1994) Positive inotropic effect of acetylcholine; role of endocardial endothelium, cGMP, nitric oxide, prostaglandins. Circulation 90: I - 649

    Google Scholar 

  42. Meulemans AL, Andries LJ, Brutsaert DL (1990) Does endocardial endothelium mediate positive inotropic response to angiotensin I and angiotensin II? Circ Res 66: 15911601

    Google Scholar 

  43. Li K, Stewart DJ, Rouleau JL (1991) Myocardial contractile actions of endothelin-1 in rat and rabbit papillary muscles. Role of endocardial endothelium. Circ Res 69: 301312

    Google Scholar 

  44. Brutsaert DL (1991) Role of endocardium in cardiac overloading and failure. Eur Heart J 11: 8–16

    Article  Google Scholar 

  45. Brutsaert DL (1989) The endocardium. Annu Rev Physiol 51: 263–273

    Article  PubMed  CAS  Google Scholar 

  46. Adams DJ, Rusko J, Van Slooten G (1993) Calcium signalling in vascular endothelial cells: Cat+ entry and release. In: Weir EK, Hume JR, Reeves JI (eds) Ion flux in pulmonary vascular control. NATO ASI series, vol 251. Plenum, New York, pp 259275

    Google Scholar 

  47. Laskey RE, Adams DJ, Johns A, Rubanyi GM, Van Breemen C (1990) Regulation of [Ca2+]i in endocardial cells by membrane potential. In: Rubanyi GM, Vanhoutte PM (eds) Endothelium-derived relaxing factors. Basel, Karger, pp 28–35

    Google Scholar 

  48. Busse R, Hecker M, Fleming I (1994) Control of nitric oxide and prostacyclin synthesis in endothelial cells. Arzneim-Forsch 44: 392–396

    CAS  Google Scholar 

  49. Laskey RE, Adams DJ, Cannell M, Van Breemen C (1992) Calcium entry-dependent oscillations of cytoplasmic calcium concentration in cultured endothelial cell mono-layers. Proc Natl Acad Sci USA 89: 1690–1694

    Article  PubMed  CAS  Google Scholar 

  50. Laskey RE, Adams DJ, Johns A, Rubanyi GM, Van Breemen C (1990) Membrane potential and Na+-K+ pump activity modulate resting and bradykinin-stimulated changes in cytosolic free calcium in cultured endothelial cells from bovine atria. J Biol Chem 265: 2613–1629

    PubMed  CAS  Google Scholar 

  51. Adams DJ (1994) Ionic channels in vascular endothelial cells. Trends Cardiovasc Med 4: 18–26

    Article  PubMed  CAS  Google Scholar 

  52. Adams DJ, Barakeh J, Laskey R, Van Breemen C (1989) Ion channels and regulation of intracellular calcium in vascular endothelial cells. FASEB J 3: 2389–2400

    PubMed  CAS  Google Scholar 

  53. Northover BJ (1980) The membrane potential of vascular endothelial cells. Adv Microcirc 9: 135–160

    CAS  Google Scholar 

  54. Fransen PF, Demolder MJM, Brutsaert DL (1995) Whole-cell membrane currents in cultured pig endocardial endothelial cells from the porcine right ventricle. Am J Physiol 258: H2036 - H2047

    Google Scholar 

  55. Smith JA, Shah AM, Lewis MJ (1991) Factors released from endocardium of the ferret and pig modulate myocardial contraction. J Physiol (Lond) 439: 1–14

    CAS  Google Scholar 

  56. Ramaciotti C, McClellan G, Sharkey A, Rose D, Weisberg A, Winegrad S (1993) Cardiac endothelial cells modulate contractility of rat heart in response to oxygen tension and coronary flow. Circ Res 72: 1044–1064

    Article  PubMed  CAS  Google Scholar 

  57. Schulz R, Smith JA, Lewis MJ, Moncada S (1991) Nitric oxide synthase in cultured endocardial cells of the pig. Br J Pharmacol 104: 21–24

    Article  PubMed  CAS  Google Scholar 

  58. Schulz R, Nava E, Moncada S (1992) Induction and potential biological relevance of Ca“-independent nitric oxide synthase in the myocardium. Br J Pharmacol 105: 575580

    Google Scholar 

  59. Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 43: 109–142

    PubMed  CAS  Google Scholar 

  60. Mohan P, Brutsaert DL, Paulus WJ, Sys SU (1996) Myocardial contractile response to nitric oxide and cGMP. Circulation 93: 1223–1229

    Article  PubMed  CAS  Google Scholar 

  61. Grocott-Mason R, Anning P, Evans H, Lewis MJ, Shah AM (1994) Modulation of left ventricular relaxation in isolated heart by endogenous nitric oxide. Am J Physiol 267: H1804 - H1813

    PubMed  CAS  Google Scholar 

  62. Paulus WJ, Vantrimpont PJ, Shah AM (1994) Acute effects of nitric oxide on left ventricular relaxation and diastolic distensibility in humans. Assessment by bicoronary sodium nitroprusside infusion. Circulation 89: 2070–2078

    Google Scholar 

  63. Shah AM, Lewis MJ, Henderson AH (1991) Effects of 8-bromo-cyclic GMP on contraction and on inotropic response of ferret cardiac muscle. J Mol Cell Cardiol 23: 55–64

    Article  PubMed  CAS  Google Scholar 

  64. Shah AM, Spurgeon HA, Sollot SJ, Talo A, Lakatta EG (1994) 8-Bromo-cGMP reduces the myofilament response to Ca“ in intact cardiac myocytes. Circ Res 74: 970–978

    Google Scholar 

  65. De Belder Al, Radomski MW, Why HJF, Richardson PJ, Bucknall CA, Salas E, Martin JF, Moncada S (1993) Nitric oxide synthase activities in human myocardium. Lancet 341: 84–85

    Article  Google Scholar 

  66. Brandt R, Nowak J, Sonnenfeld T (1984) Prostaglandin formation from exogenous precursor in homogenates of human cardiac tissue. Basic Res Cardiol 79: 135–141

    Article  PubMed  CAS  Google Scholar 

  67. Mebazaa A, Martin LD, Robotham JL, Maeda K, Gabrielson EW, Wetzel RC (1993) Right and left ventricular cultured endocardial endothelium produces prostacyclin and PGE2. J Mol Cell Cardiol 25: 245–248

    Article  PubMed  CAS  Google Scholar 

  68. Mebazaa A, Wetzel R, Cherian M, Abraham M (1995) Comparison between endocardial and great vessel endothelial cells: morphology, growth, and prostaglandin release. Am J Physiol 268: H250 - H259

    PubMed  CAS  Google Scholar 

  69. Mohan P, Brutsaert DL, Sys SU (1995) Myocardial performance is modulated by interaction of cardiac endothelium-derived nitric oxide and prostaglandins. Cardiovasc Res 29: 637–640

    PubMed  CAS  Google Scholar 

  70. Davenport AP, Nunez DJ, Hall A, Kaumann AK, Brown MJ (1989) Autoradiographical localization of binding sites for porcine (125I)endothelin-1 in humans, pigs, and rats: functional relevance in humans. J Cardiovasc Pharmacol 161: 1252–1259

    Google Scholar 

  71. Mebazaa A, Mayoux E, Maeda K, Martin LD, Lakatta EG, Robotham JL, Shah AM (1993) Paracrine effects of endocardial endothelial cells on myocyte contraction mediated via endothelin. Am J Physiol 265: H1841 - H1846

    PubMed  CAS  Google Scholar 

  72. Evans HG, Lewis MJ, Shah AM (1994) Modulation of myocardial relaxation by basal release of endothelin from endocardial endothelium. Cardiovasc Res 28: 1694–1699

    Article  PubMed  CAS  Google Scholar 

  73. Wang J, Paik G, Morgan J (1991) Endothelin enhances myofilament Ca“ responsiveness in aequorin-loaded ferret myocardium. Circ Res 69: 582–589

    Article  PubMed  CAS  Google Scholar 

  74. Kramer BK, Smith TW, Kelly RA (1991) Endothelin and increased contractility in adult rat ventricular myocytes: role of intracellular alkalosis induced by activation of the protein kinase C-dependent Na’-H’-exchanger. Circ Res 68: 269–279

    Article  PubMed  CAS  Google Scholar 

  75. Ono K, Eto K, Sakamoto A, Masaki T, Shihata K, Sada T, Hashimoto K, Tsujimoto G (1995) Negative chronotropic effect of endothelin-1 mediated through ET-A receptors in guinea pig atria. Circ Res 76: 284–292

    Article  PubMed  CAS  Google Scholar 

  76. Ito H, Hirata Y, Hiroe M, Tsujino M, Adachi S, Takamoto T, Nitta M, Taniguchi K, Marumo F (1991) Endothelin-1 induces hypertrophy with enhanced expression of muscle specific genes in cultured neonatal rat cardiomyocytes. Circ Res 69: 209–215

    Article  PubMed  CAS  Google Scholar 

  77. Löscher TF, Boulanger CM, Yang Z, Noll G, Dohi Y (1993) Interactions between endothelium-derived relaxing and contracting factors in health and cardiovascular disease. Circulation 87 (suppl V): V36 - V44

    Google Scholar 

  78. Wang J, Morgan JP (1992) Endothelin reverses the effects of acidosis on the intracellular Ca“ transient and contractility in ferret myocardium. Circ Res 71: 631–639

    Article  PubMed  CAS  Google Scholar 

  79. James AF, Xie L, Fujitani Y, Hayashi S, Hone M (1994) Inhibition of cardiac protein kinase A-dependent chloride conductance by endothelin-1. Nature 370: 297–300

    Article  PubMed  CAS  Google Scholar 

  80. Ono K, Tsujimoto G, Sakamoto A, Eto K, Masaki T, Ozaki Y, Satake M (1994) Endothelin-A receptor mediates cardiac inhibition by regulating calcium and potassium currents. Nature 370: 301–304

    Article  PubMed  CAS  Google Scholar 

  81. Fransen P, Andries LJ, Van Bedaf D, Demolder M, Sys SU (1996) Cell coupling in cultured endocardial endothelium. Eur J Physiol 431: R323

    Google Scholar 

  82. Ito H, Matsuda H, Noma A (1993) Ion channels in the luminal membrane of endothelial cells of the bull-frog heart. Jpn J Physiol 43: 191–206

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Medicine Antwerp University, Antwerp, Belgium

    Gilles W. De Keulenaer, Luc J. Andries, Paul F. Fransen, Puneet Mohan, Gregory Kaluza, Dirk L. Brutsaert & Stanislas U. Sys

  2. Department of Medicine, University of Montreal, Montreal, Canada

    Jean L. Rouleau

Authors
  1. Gilles W. De Keulenaer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luc J. Andries
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul F. Fransen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Puneet Mohan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gregory Kaluza
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jean L. Rouleau
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dirk L. Brutsaert
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stanislas U. Sys
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. First Department of Internal Medicine, Fukushima Medical College, Hikariga-oka 1, 960-12, Fukushima, Japan

    Yukio Maruyama M.D., Ph.D. (Professor and Chairman) (Professor and Chairman)

  2. First Department of Medicine, Osaka University School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565, Japan

    Masatsugu Hori M.D., Ph.D. (Chief) (Chief)

  3. College of Veterinary Medicine, Auburn University, 106 Greene Hall, 36849-5517, Auburn, AL, USA

    Joseph S. Janicki Ph.D. (Professor, Associate Dean of Research and Graduate Studies) (Professor, Associate Dean of Research and Graduate Studies)

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Japan

About this chapter

Cite this chapter

De Keulenaer, G.W. et al. (1997). Endocardial—Myocardial Interaction. In: Maruyama, Y., Hori, M., Janicki, J.S. (eds) Cardiac-Vascular Remodeling and Functional Interaction. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67041-4_13

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-67041-4_13

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-67043-8

  • Online ISBN: 978-4-431-67041-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation