Skip to main content
SpringerLink
Log in

Role of Connective Tissue Growth Factor in Cardiac Fibrosis

  • Chapter
  • First Online:
CCN Proteins in Health and Disease

  • 412 Accesses

Abstract

Cardiac fibrosis is an important pathogenic feature of the remodeling process that occurs in heart failure and myocardial infarction. This process is triggered by a number of signaling pathways that result in excessive production and deposition of extracellular matrix (ECM). Connective Tissue Growth factor (CTGF, CCN2), a member of CCN (Cyr61, Ctgf, Nov) family, is a multifunctional protein that is expressed in both cardiac myocytes and fibroblasts that is a key regulator of the fibrotic response. CTGF is a critical downstream target of transforming growth factor-β (TGF-β) signaling in the cardiovascular system. Kruppel-like factor 15 (KLF15) is a transcription factor that is expressed in both cardiomyocytes and cardiac fibroblasts and serves as a negative regulator of pathologic remodeling. Our group has demonstrated that KLF15 inhibits cardiac hypertrophy in response to pressure overload. Recently, we have shown that KLF15 is a novel negative regulator of CTGF expression in the heart via its ability to counteract Smad signaling at the CTGF promoter. From a clinical standpoint, progress has been made in utilizing CTGF levels as a biomarker for fibrotic diseases. In this chapter, we will summarize studies of CTGF in heart disease and discuss its importance in cardiac remodeling. In addition, potential therapeutic strategies targeting CTGF will be discussed.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
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

  • Abreu J.G., Ketpura N.I., Reversade B., De Robertis E.M. (2002). Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta. Nat Cell Biol 4: 599–604.

    PubMed  CAS  Google Scholar 

  • Ahmed M.S., Oie E., Vinge L.E., Yndestad A., Oystein Andersen G., Andersson Y., Attramadal T., Attramadal H. (2004). Connective tissue growth factor – a novel mediator of angiotensin II-stimulated cardiac fibroblast activation in heart failure in rats. J Mol Cell Cardiol 36: 393–404.

    Article  PubMed  CAS  Google Scholar 

  • Atkins G.B., Jain M.K. (2007). Role of Kruppel-like transcription factors in endothelial biology. Circ Res 100: 1686–1695.

    Article  PubMed  CAS  Google Scholar 

  • Banerjee I., Yekkala K., Borg T.K., Baudino T.A. (2006). Dynamic interactions between myocytes, fibroblasts, and extracellular matrix. Ann NY Acad Sci 1080: 76–84.

    Article  PubMed  CAS  Google Scholar 

  • Bhatt N., Baran C.P., Allen J., Magro C., Marsh C.B. (2006). Promising pharmacologic innovations in treating pulmonary fibrosis. Curr Opin Pharmacol 6: 284–292.

    Article  PubMed  CAS  Google Scholar 

  • Black A.R., Black J.D., Azizkhan-Clifford J. (2001). Sp1 and kruppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol 188: 143–160.

    Article  PubMed  CAS  Google Scholar 

  • Bradham D.M., Igarashi A., Potter R.L., Grotendorst G.R. (1991). Connective tissue growth factor: a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10. J Cell Biol 114: 1285–1294.

    Article  PubMed  CAS  Google Scholar 

  • Brand T., Schneider M.D. (1995). The TGF beta superfamily in myocardium: ligands, receptors, transduction, and function. J Mol Cell Cardiol 27: 5–18.

    Article  PubMed  CAS  Google Scholar 

  • Braunwald E. (2008). Biomarkers in heart failure. N Engl J Med 358: 2148–2159.

    Article  PubMed  CAS  Google Scholar 

  • Campbell S.E., Katwa L.C. (1997). Angiotensin II stimulated expression of transforming growth factor-beta1 in cardiac fibroblasts and myofibroblasts. J Mol Cell Cardiol 29: 1947–1958.

    Article  PubMed  CAS  Google Scholar 

  • Carvajal G., Rodriguez-Vita J., Rodrigues-Diez R., Sanchez-Lopez E., Ruperez M., Cartier C., Esteban V., Ortiz A., Egido J., Mezzano S.A., Ruiz-Ortega M. (2008). Angiotensin II activates the Smad pathway during epithelial mesenchymal transdifferentiation. Kidney Int 74: 585–595.

    Article  PubMed  CAS  Google Scholar 

  • Chen M.M., Lam A., Abraham J.A., Schreiner G.F., Joly A.H. (2000). CTGF expression is induced by TGF- beta in cardiac fibroblasts and cardiac myocytes: a potential role in heart fibrosis. J Mol Cell Cardiol 32: 1805–1819.

    Article  PubMed  CAS  Google Scholar 

  • Chen Y., Blom I.E., Sa S., Goldschmeding R., Abraham D.J., Leask A. (2002). CTGF expression in mesangial cells: involvement of SMADs, MAP kinase, and PKC. Kidney Int 62: 1149–1159.

    Article  PubMed  CAS  Google Scholar 

  • Chin M.T. (2008). KLF15 and cardiac fibrosis: the heart thickens. J Mol Cell Cardiol 45: 165–167.

    Article  PubMed  CAS  Google Scholar 

  • Dang D.T., Zhao W., Mahatan C.S., Geiman D.E., Yang V.W. (2002). Opposing effects of Kruppel-like factor 4 (gut-enriched Kruppel-like factor) and Kruppel-like factor 5 (intestinal-enriched Kruppel-like factor) on the promoter of the Kruppel-like factor 4 gene. Nucl Acids Res 30: 2736–2741.

    Article  PubMed  CAS  Google Scholar 

  • Daniels A., van Bilsen M., Goldschmeding R., van der Vusse G.J., van Nieuwenhoven F.A. (2009). Connective tissue growth factor and cardiac fibrosis. Acta Physiol (Oxf), 195: 321–338.

    Article  CAS  Google Scholar 

  • Duisters R.F., Tijsen A.J., Schroen B., Leenders J.J., Lentink V., van der Made I., Herias V., van Leeuwen R.E., Schellings M.W., Barenbrug P., Maessen J.G., Heymans S., Pinto Y.M., Creemers E.E. (2009). miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Cir Res 104: 170–178, 176p following 178.

    Article  CAS  Google Scholar 

  • Feinberg M.W., Lin Z., Fisch S., Jain M.K. (2004). An emerging role for Kruppel-like factors in vascular biology. Trends Cardiovasc Med 14: 241–246.

    Article  PubMed  CAS  Google Scholar 

  • Finckenberg P., Inkinen K., Ahonen J., Merasto S., Louhelainen M., Vapaatalo H., Muller D., Ganten D., Luft F., Mervaala E. (2003). Angiotensin II induces connective tissue growth factor gene expression via calcineurin-dependent pathways. Am J Pathol 163: 355–366.

    PubMed  CAS  Google Scholar 

  • Finckenberg P., Lassila M., Inkinen K., Pere A.K., Krogerus L., Lindgren L., Mervaala E., Vapaatalo H., Nurminen M.L., Ahonen J. (2001). Cyclosporine induces myocardial connective tissue growth factor in spontaneously hypertensive rats on high-sodium diet. Transplantation 71: 951–958.

    Article  PubMed  CAS  Google Scholar 

  • Fisch S., Gray S., Heymans S., Haldar S.M., Wang B., Pfister O., Cui L., Kumar A., Lin Z., Sen-Banerjee S., Das H., Petersen C.A., Mende U., Burleigh B.A., Zhu Y., Pinto Y.M., Liao R., Jain M.K. (2007). Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy. Proc Nat Acad Sci U S Am 104: 7074–7079.

    Article  CAS  Google Scholar 

  • Fisher N.D., Allan D.R., Gaboury C.L., Hollenberg N.K. (1995). Intrarenal angiotensin II formation in humans. Evidence from renin inhibition. Hypertension 25: 935–939.

    CAS  Google Scholar 

  • Gray M.O., Long C.S., Kalinyak J.E., Li H.T., Karliner J.S. (1998). Angiotensin II stimulates cardiac myocyte hypertrophy via paracrine release of TGF-beta 1 and endothelin-1 from fibroblasts. Cardiovasc Res 40: 352–363.

    Article  PubMed  CAS  Google Scholar 

  • Gray S., Feinberg M.W., Hull S., Kuo C.T., Watanabe M., Sen-Banerjee S., DePina A., Haspel R., Jain M.K. (2002). The Kruppel-like factor KLF15 regulates the insulin-sensitive glucose transporter GLUT4. J Biol Chem 277: 34322–34328.

    Article  PubMed  CAS  Google Scholar 

  • Gray S., Wang B., Orihuela Y., Hong E.G., Fisch S., Haldar S., Cline G.W., Kim J.K., Peroni O.D., Kahn B.B., Jain M.K. (2007). Regulation of Gluconeogenesis by Kruppel-like Factor 15. Cell Metabol 5: 305–312.

    Article  CAS  Google Scholar 

  • Grotendorst G.R., Okochi H., Hayashi N. (1996). A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene. Cell Growth Differ 7: 469–480.

    PubMed  CAS  Google Scholar 

  • Guo P., Nishiyama A., Rahman M., Nagai Y., Noma T., Namba T., Ishizawa M., Murakami K., Miyatake A., Kimura S., Mizushige K., Abe Y., Ohmori K., Kohno M. (2006). Contribution of reactive oxygen species to the pathogenesis of left ventricular failure in Dahl salt-sensitive hypertensive rats: effects of angiotensin II blockade. J Hyperten 24: 1097–1104.

    Article  CAS  Google Scholar 

  • Haldar S.M., Ibrahim O.A., Jain M.K. (2007). Kruppel-like Factors (KLFs) in muscle biology. J Mol Cell Cardiol 43: 1–10.

    Article  PubMed  CAS  Google Scholar 

  • Hayata N., Fujio Y., Yamamoto Y., Iwakura T., Obana M., Takai M., Mohri T., Nonen S., Maeda M., Azuma J. (2008). Connective tissue growth factor induces cardiac hypertrophy through Akt signaling. Biochem Biophys Res Commun 370: 274–278.

    Article  PubMed  CAS  Google Scholar 

  • Itoh S., Ericsson J., Nishikawa J., Heldin C.H., ten Dijke P. (2000). The transcriptional co-activator P/CAF potentiates TGF-beta/Smad signaling. Nucl Acids Res 28: 4291–4298.

    Article  PubMed  CAS  Google Scholar 

  • Iwanciw D., Rehm M., Porst M., Goppelt-Struebe M. (2003). Induction of connective tissue growth factor by angiotensin II: integration of signaling pathways. Arterioscler Thromb Vasc Biol 23: 1782–1787.

    Article  PubMed  CAS  Google Scholar 

  • Jain M.K., Ridker P.M. (2005). Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Dis 4: 977–987.

    Article  CAS  Google Scholar 

  • Jugdutt B.I. (2003). Ventricular remodeling after infarction and the extracellular collagen matrix: when is enough enough? Circulation 108: 1395–1403.

    Article  PubMed  Google Scholar 

  • Khan R., Sheppard R. (2006). Fibrosis in heart disease: understanding the role of transforming growth factor-beta in cardiomyopathy, valvular disease and arrhythmia. Immunology 118: 10–24.

    Article  PubMed  CAS  Google Scholar 

  • Koitabashi N., Arai M., Kogure S., Niwano K., Watanabe A., Aoki Y., Maeno T., Nishida T., Kubota S., Takigawa M., Kurabayashi M. (2007). Increased connective tissue growth factor relative to brain natriuretic peptide as a determinant of myocardial fibrosis. Hypertension 49: 1120–1127.

    Article  PubMed  CAS  Google Scholar 

  • Koitabashi N., Arai M., Niwano K., Watanabe A., Endoh M., Suguta M., Yokoyama T., Tada H., Toyama T., Adachi H., Naito S., Oshima S., Nishida T., Kubota S., Takigawa M., Kurabayashi M. (2008). Plasma connective tissue growth factor is a novel potential biomarker of cardiac dysfunction in patients with chronic heart failure. Eur J Heart Fail 10: 373–379.

    Article  PubMed  CAS  Google Scholar 

  • Leask A., Parapuram S.K., Shi-Wen X., Abraham D.J. (2009). Connective tissue growth factor (CTGF, CCN2) gene regulation: a potent clinical bio-marker of fibroproliferative disease? J Cell Commun Signal 3: 89–94.

    Google Scholar 

  • Lee A.A., Dillmann W.H., McCulloch A.D., Villarreal F.J. (1995). Angiotensin II stimulates the autocrine production of transforming growth factor-beta 1 in adult rat cardiac fibroblasts. J Mol Cell Cardiol 27: 2347–2357.

    Article  PubMed  CAS  Google Scholar 

  • Li H.L., Liu C., de Couto G., Ouzounian M., Sun M., Wang A.B., Huang Y., He C.W., Shi Y., Chen X., Nghiem M.P., Liu Y., Chen M., Dawood F., Fukuoka M., Maekawa Y., Zhang L., Leask A., Ghosh A.K., Kirshenbaum L.A., Liu P.P. (2008). Curcumin prevents and reverses murine cardiac hypertrophy. J Clin Invest 118: 879–893.

    Article  PubMed  CAS  Google Scholar 

  • Maisch B. (1995). Extracellular matrix and cardiac interstitium: restriction is not a restricted phenomenon. Herz 20: 75–80.

    PubMed  CAS  Google Scholar 

  • Manabe I., Shindo T., Nagai R. (2002). Gene expression in fibroblasts and fibrosis: involvement in cardiac hypertrophy. Circ Res 91: 1103–1113.

    Article  PubMed  CAS  Google Scholar 

  • Mori T., Sakaue H., Iguchi H., Gomi H., Okada Y., Takashima Y., Nakamura K., Nakamura T., Yamauchi T., Kubota N., Kadowaki T., Matsuki Y., Ogawa W., Hiramatsu R., Kasuga M. (2005). Role of Kruppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis. J Biol Chem 280: 12867–12875.

    Article  PubMed  CAS  Google Scholar 

  • Moriguchi Y., Matsubara H., Mori Y., Murasawa S., Masaki H., Maruyama K., Tsutsumi Y., Shibasaki Y., Tanaka Y., Nakajima T., Oda K., Iwasaka T. (1999). Angiotensin II-induced transactivation of epidermal growth factor receptor regulates fibronectin and transforming growth factor-beta synthesis via transcriptional and posttranscriptional mechanisms. Circ Res 84: 1073–1084.

    PubMed  CAS  Google Scholar 

  • Nishida T., Kondo S., Maeda A., Kubota S., Lyons K.M., Takigawa M. (2009). CCN family 2/connective tissue growth factor (CCN2/CTGF) regulates the expression of Vegf through Hif-1alpha expression in a chondrocytic cell line, HCS-2/8, under hypoxic condition. Bone 44: 24–31.

    Article  PubMed  CAS  Google Scholar 

  • Ohnishi H., Oka T., Kusachi S., Nakanishi T., Takeda K., Nakahama M., Doi M., Murakami T., Ninomiya Y., Takigawa M., Tsuji T. (1998). Increased expression of connective tissue growth factor in the infarct zone of experimentally induced myocardial infarction in rats. J Mol Cell Cardiol 30: 2411–2422.

    Article  PubMed  CAS  Google Scholar 

  • Peng H., Carretero O.A., Brigstock D.R., Oja-Tebbe N., Rhaleb N.E. (2003). Ac-SDKP reverses cardiac fibrosis in rats with renovascular hypertension. Hypertension 42: 1164–1170.

    Article  PubMed  CAS  Google Scholar 

  • Perbal B. (2004). CCN proteins: multifunctional signalling regulators. Lancet 363: 62–64.

    Article  PubMed  CAS  Google Scholar 

  • Powell D.W., Mifflin R.C., Valentich J.D., Crowe S.E., Saada J.I., West A.B. (1999). Myofibroblasts. I. Paracrine cells important in health and disease. Am J Physiol 277, C1–9.

    PubMed  CAS  Google Scholar 

  • Recchia A.G., Filice E., Pellegrino D., Dobrina A., Cerra M.C., Maggiolini M. (2009). Endothelin-1 induces connective tissue growth factor expression in cardiomyocytes. J Mol Cell Cardiol 46: 352–359.

    Article  PubMed  CAS  Google Scholar 

  • Rosenkranz S. (2004). TGF-beta1 and angiotensin networking in cardiac remodeling. Cardiovasc Res 63: 423–432.

    Article  PubMed  CAS  Google Scholar 

  • Sadoshima J., Xu Y., Slayter H.S., Izumo S. (1993). Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 75: 977–984.

    Article  PubMed  CAS  Google Scholar 

  • Sano M., Minamino T., Toko H., Miyauchi H., Orimo M., Qin Y., Akazawa H., Tateno K., Kayama Y., Harada M., Shimizu I., Asahara T., Hamada H., Tomita S., Molkentin J.D., Zou Y., Komuro I. (2007). p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload. Nature 446: 444–448.

    Article  PubMed  CAS  Google Scholar 

  • Schmierer B., Hill C.S. (2007). TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol 8: 970–982.

    Article  PubMed  CAS  Google Scholar 

  • Schnee J.M., Hsueh W.A. (2000). Angiotensin II, adhesion, and cardiac fibrosis. Cardiovasc Res 46: 264–268.

    Article  PubMed  CAS  Google Scholar 

  • Shi Y., Massague J. (2003). Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113: 685–700.

    Article  PubMed  CAS  Google Scholar 

  • Sun Y., Zhang J.Q., Zhang J., Lamparter S. (2000). Cardiac remodeling by fibrous tissue after infarction in rats. J Lab Clin Med 135: 316–323.

    Article  PubMed  CAS  Google Scholar 

  • ten Dijke P., Arthur H.M. (2007). Extracellular control of TGFbeta signalling in vascular development and disease. Nat Rev Mol Cell Biol 8: 857–869.

    Article  PubMed  CAS  Google Scholar 

  • Tomasek J.J., Gabbiani G., Hinz B., Chaponnier C., Brown R.A. (2002). Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 3: 349–363.

    Article  PubMed  CAS  Google Scholar 

  • Tomita H., Egashira K., Ohara Y., Takemoto M., Koyanagi M., Katoh M., Yamamoto H., Tamaki K., Shimokawa H., Takeshita A. (1998). Early induction of transforming growth factor-beta via angiotensin II type 1 receptors contributes to cardiac fibrosis induced by long-term blockade of nitric oxide synthesis in rats. Hypertension 32: 273–279.

    PubMed  CAS  Google Scholar 

  • van Rooij E., Marshall W.S., Olson E.N. (2008). Toward microRNA-based therapeutics for heart disease: the sense in antisense. Circ Res 103: 919–928.

    Article  PubMed  CAS  Google Scholar 

  • van Vliet J., Crofts L.A., Quinlan K.G., Czolij R., Perkins A.C., Crossley M. (2006). Human KLF17 is a new member of the Sp/KLF family of transcription factors. Genomics 87: 474–482.

    Article  PubMed  CAS  Google Scholar 

  • Wahab N.A., Weston B.S., Mason R.M. (2005). Modulation of the TGFbeta/Smad signaling pathway in mesangial cells by CTGF/CCN2. Exp Cell Res 307: 305–314.

    Article  PubMed  CAS  Google Scholar 

  • Wang B., Haldar S.M., Lu Y., Ibrahim O.A., Fisch S., Gray S., Leask A., Jain M.K. (2008). The Kruppel-like factor KLF15 inhibits connective tissue growth factor (CTGF) expression in cardiac fibroblasts. J Mol Cell Cardiol 45: 193–197.

    Article  PubMed  CAS  Google Scholar 

  • Wang W., Huang X.R., Canlas E., Oka K., Truong L.D., Deng C., Bhowmick N.A., Ju W., Bottinger E.P., Lan H.Y. (2006). Essential role of Smad3 in angiotensin II-induced vascular fibrosis. Circ Res 98: 1032–1039.

    Article  PubMed  CAS  Google Scholar 

  • Wenzel S., Taimor G., Piper H.M., Schluter K.D. (2001). Redox-sensitive intermediates mediate angiotensin II-induced p38 MAP kinase activation, AP-1 binding activity, and TGF-beta expression in adult ventricular cardiomyocytes. FASEB J 15: 2291–2293.

    PubMed  CAS  Google Scholar 

  • Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. (1988). A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332: 411–415.

    Article  PubMed  CAS  Google Scholar 

  • Zaglia T., Dedja A., Candiotto C., Cozzi E., Schiaffino S., Ausoni S. (2009). Cardiac interstitial cells express GATA4 and control dedifferentiation and cell cycle re-entry of adult cardiomyocytes. J Mol Cell Cardiol 46: 653–682.

    Google Scholar 

  • Zhang W., Shields J.M., Sogawa K., Fujii-Kuriyama Y., Yang V.W. (1998). The gut-enriched Kruppel-like factor suppresses the activity of the CYP1A1 promoter in an Sp1-dependent fashion. J Biol Chem 273: 17917–17925.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

Our research is supported by NIH grants HL72952, HL75427, HL76754, HL086548, HL084154 and P01 HL48743 (to M.K.J.); and HL 086614 (to S.H.); and Dominic Visconsi Scholarship Award (to S.H.); and American Heart Association Postdoctoral Fellowship 0725297B (to D.K.); and a Kanae Foundation for the Promotion of Medical Science grant (to D.K.).

Author information

Authors and Affiliations

  1. University Hospitals Harrington-McLaughlin Heart and Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, 2103 Cornell Road, Room 4-522, Cleveland, OH, 44106, USA

    Daiji Kawanami, Saptarsi M. Haldar & Mukesh K. Jain

Authors
  1. Daiji Kawanami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Saptarsi M. Haldar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mukesh K. Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mukesh K. Jain .

Editor information

Editors and Affiliations

  1. Med Sci-I 6447, Ann Arbor, 48109, USA

    Annick Perbal

  2. Shikata-Cho 2-5-1, Okayama, 700-8525, Japan

    Masaharu Takigawa

  3. Palais du Grand Large, International CCN Society, Saint-Malo, France

    Bernard Perbal

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Kawanami, D., Haldar, S.M., Jain, M.K. (2010). Role of Connective Tissue Growth Factor in Cardiac Fibrosis. In: Perbal, A., Takigawa, M., Perbal, B. (eds) CCN Proteins in Health and Disease. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3779-4_10

Download citation

Publish with us

Policies and ethics

Search

Navigation