Skip to main content
SpringerLink
Log in
Book cover

Heart Hypertrophy and Failure pp 79–92Cite as

Intracellular Signaling and Genetic Reprogramming During Development of Hypertrophy in Cultured Cardiomyocytes

  • Chapter

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 169))

Abstract

Cardiac hypertrophy is an adaptation of the heart to chronically increased workload, for example, during hemodynamic overload or after infarction. Hypertrophy is brought about by enlargement of cardiac myocytes rather than by proliferation of the cells. Although the initial outcome is a compensatory growth of the heart, prolonged development of hypertrophy leads to gross changes in phenotype of the heart muscle as well, ultimately resulting in heart failure [1,2]. For instance, in the ventricle the potent vasodilator atrial natriuretic factor (ANF) is reexpressed in the compensatory phase of hypertrophy, which might be beneficial during hemodynamic overload. In the sarcomeric units the fetal isozyme of myosin heavy chain, which has a lower velocity of ATP cycling, is reexpressed, thereby improving the economy of contraction as less energy is dissipated as heat. On the other hand, hypertrophy ultimately has detrimental effects on the performance of the heart. Not only does the architecture of the muscle change (remodeling), but contractility and relaxation of the heart arc impaired as well. The latter phenomena may in part be explained by changes in the expression of genes coding for components of the Ca2+ handling systems in the heart muscle cell [2–4]. In this phase of the hypertrophic response, some cells start deteriorating and ultimately die, thereby increasing the workload of the remaining cells. Ultimately, heart failure develops, which gives rise to serious circulatory problems in response to the impaired pump function.

This is a preview of subscription content, 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   259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   379.99
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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bohcler KR, Schwartz K. 1992. Gene expression in cardiac hypertrophy. Trends Cardiovasc Med 2:176–182.

    Article  Google Scholar 

  2. Schwartz K, Carrier L, Mercadier J-J, Lompre A-M, Boheler KR. 1993. Molecular pheno-type of the hypertrophicd and failing myocardium. Circulation 87:VII.5–VII. 10.

    Google Scholar 

  3. Arai M, Matsui H, Periasamy M. 1994. Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure. Circulation 74:555–564.

    CAS  Google Scholar 

  4. Sharma HS, Verdouw PD, Lamers JMJ. 1994. Involvement of sarcoplasmic reticulum calcium pump in myocardial contractile dysfunction: Comparison between chronic pressure-overload and stunning. Cardiovasc Drugs Therapy 8:461–468.

    Article  CAS  Google Scholar 

  5. Van Heugten HAA, de Jonge HW, Bezstarosti K, Sharma HS, Verdouw PD, Lamers JMJ. 1995. Intracellular signalling and genetic reprogramming during agonist-induced hypertrophy of cardiomyocytes. Ann NY Acad Sci 752:343–352.

    Article  PubMed  Google Scholar 

  6. Simpson P. 1985. Stimulation of hypertrophy of cultured neonatal rat heart cells through an α1-Adrenergic receptor and induction of beating through an α1- and β1-adrenergic receptor interaction. Evidence for independent regulation of growth and beating. Circ Res 56: 884–894.

    PubMed  CAS  Google Scholar 

  7. Meidell RS, Sen A, Henderson SA, Slahetka MF, Chien KR. 1986. α1-Adrenergic stimulation of rat myocardial cells increases protein synthesis. Am J Physiol 251:H1076–H1084.

    PubMed  CAS  Google Scholar 

  8. Iwaki K, Sukhatme VP, Shubeita HE, Chien KR. 1990. α- and β-adrenergic stimulation induces distinct patterns of immediate early gene expression in neonatal rat myocardial cells. Fos/jun expression is associated with sarcomere assembly; Egr-1 induction is primarily an α1-mediated response. J Biol Chem 265:13809–13817.

    PubMed  CAS  Google Scholar 

  9. Waspe LE, Ordahl CP, Simpson PC. 1990. The cardiac α-myosin heavy chain isogene is induced selectively in α1-adrenergic receptor-stimulated hypertrophy of cultured rat heart myocytes. J Clin Invest 85:1206–1214.

    Article  PubMed  CAS  Google Scholar 

  10. Knowlton KU, Baracchini E, Ross RS, Harris AN, Henderson SA, Evans SM, Glembotski CC, Chien KR. 1991. Co-regulation of the atrial natriuretic factor and cardiac myosin light chain-2 genes during α-adrenergic stimulation of neonatal rat ventricular cells. Identification of cis sequences within an embryonic and a constitutive contractile protein gene which mediate inducible expression. J Biol Chem 266:7759–7768.

    PubMed  CAS  Google Scholar 

  11. Zierhut W, Zimmer HG. 1989. Significance of myocardial α- and β-adrenoceptors in catecholamine-induced cardiac hypertrophy. Circ Res 65:1417–1425.

    PubMed  CAS  Google Scholar 

  12. Sadoshima J-I, Izumo S. 1993. Molecular characterization of the angiotensin II-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT, receptor subtype. Circ Res 73:413–423.

    PubMed  CAS  Google Scholar 

  13. Sadoshima J-I, Izumo S. 1993. Signal transduction pathways of angiotensin II-induced c-fos gene expression in cardiac myocytes in vitro. Roles of phospholipid-derived second messengers. Circ Res 73:424–438.

    PubMed  CAS  Google Scholar 

  14. Shubeita HE, McDonough PM, Harris AN, Knowlton KU, Glembotski CG, Brown JH, Chien KR. 1990. Endothelin induction of inositol phospholipid hydrolysis, sarcomere assembly, and cardiac gene expression in ventricular myocytes. A paracrine mechanism for myocardial cell hypertrophy. J Biol Chem 265: 20555–20562.

    PubMed  CAS  Google Scholar 

  15. Suzuki T, Hoshi H, Sasaki H, Mitsui Y. 1990. Endothelin stimulates hypertrophy and contractility of neonatal rat cardiac myocytes in a serum-free medium II. J Cardiovasc Pharmacol 17(Suppl 7):S182-S187.

    Google Scholar 

  16. 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.

    PubMed  CAS  Google Scholar 

  17. Wang DL, Chen JJ, Shin NL, Kao YC, Hsu KH, Huang WU, Liew CC. 1992. Endothelin stimulates cardiac α- and β-myosin heavy chain gene expression. Biochem Biophys Res Commun 183:1260–1265.

    Article  PubMed  CAS  Google Scholar 

  18. Chien WW, Mohabir R, Clusin WT. 1990. Effect of thrombin on calcium homeostasis in chick embryonic heart cells. Receptor-operated calcium entry with inositol trisphosphate and a pertussis toxin-sensitive G protein as second messengers. J Clin Invest 85:1436–1443.

    Article  PubMed  CAS  Google Scholar 

  19. Glembotski CC, Irons CE, Krown KA, Murray SF, Sprenkle AB, Sei CA. 1993. Myocardial α-thrombin receptor activation induces hypertrophy and increases atrial natriuretic factor gene expression. J Biol Chem 268:20646–20652.

    PubMed  CAS  Google Scholar 

  20. Fuller SJ, Mynett JR, Sugden PH. 1992. Stimulation of cardiac protein synthesis by insulinlike growth factors. Biochem J 282:85–90.

    PubMed  CAS  Google Scholar 

  21. Ito H, Hiroe M, Hirata Y, Tsujino M, Adachi S, Shihiri M, Koike A, Nogami A, Marumo F. 1993. Insulinlike growth factor-1 induces hypertrophy with enhanced expression of muscle specific genes in cultured rat cardiomyocytes. Circulation 87:1715–1721.

    PubMed  CAS  Google Scholar 

  22. Adachi S, Ito H, Akimoto H, Tanaka M, Fujisaki H, Marumo F, Hiroe M. 1994. Insulinlike growth factor-II induces hypertrophy with increased expression of muscle specific genes in cultured rat cardiomyocytes. J Mol Cell Cardiol 26:789–795.

    Article  PubMed  CAS  Google Scholar 

  23. Parker TG, Packer SE, Schneider MD. 1990. Peptide growth factors can provoke fetal contractile protein gene expression in rat cardiac myocytes. J Clin Invest 85:507–514.

    Article  PubMed  CAS  Google Scholar 

  24. Parker TG, Chow K-L, Schwartz RJ, Schneider MD. 1990. Differential regulation of skeletal α-actin transcription in cardiac muscle by two fibroblast growth factors. Proc Natl Acad Sci USA 87:7066–7070.

    Article  PubMed  CAS  Google Scholar 

  25. Bogoyevitch MA, Glennon PE, Andersson MB, Clerk A, Lazou A, Marshall CJ, Parker PJ, Sugden PH. 1994. Endothelin-1 and fibroblast growth factors stimulate the mitogen-activated protein kinase signaling cascade in cardiac myocytes. The potential role of the cascade in the integration of two signalling pathways leading to cardiac hypertrophy. J Biol Chem 269: 1110–1119.

    PubMed  CAS  Google Scholar 

  26. Yamada M, Hamamori Y, Akita H, Yokoyama M. 1992. P2-purinoceptor activation stimulates phosphoinositide hydrolysis and inhibits accumulation of cAMP in cultured ventricular myocytes. Circ Res 70:477–485.

    PubMed  CAS  Google Scholar 

  27. Zheng J-S, Boluyt MO, O’Neil L, Crow MT, Lakatta EG. 1994. Extracellular ATP induces immediate-early gene expression but not cellular hypertrophy in neonatal cardiac myocytes. Circ Res 74:1034–1041.

    PubMed  CAS  Google Scholar 

  28. Komuro I, Kaida T, Shibazaki Y, Kurabayashi M, Katoh Y, Hoh E, Takaku F, Yazaki Y. 1990. Stretching cardiac myocytes stimulates protooncogene expression. J Biol Chem 265: 3595–3598.

    PubMed  CAS  Google Scholar 

  29. Komuro I, Katoh Y, Kaida T, Shibazaki Y, Kurabayashi M, Hoh E, Takaku F, Yazaki Y. 1991. Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes. Possible role of protein kinase C activation. J Biol Chem 266: 1265–1268.

    PubMed  CAS  Google Scholar 

  30. Sadoshima J-I, Jahn L, Takahashi T, Kulik TJ, Izumo S. 1992. Molecular characterization of the stretch-induced adaptation of cultured cardiac cells. An in vitro model of load-induced cardiac hypertrophy. J Biol Chem 267:10551–10560.

    PubMed  CAS  Google Scholar 

  31. Sadoshima J-I, Izumo S. 1993. Mechanical stretch rapidly activates multiple signal transduction pathways in cardiac myocytes: Potential involvement of an autocrine/paracrine mechanism. EMBO J 12:1681–1692.

    PubMed  CAS  Google Scholar 

  32. McDermott PJ, Morgan HE. 1989. Contraction modulates the capacity for protein synthesis during growth of neonatal heart cells in culture. Circ Res 64:542–553.

    PubMed  CAS  Google Scholar 

  33. McDonough PM, Glembotski CC. 1992. Induction of atrial natriuretic factor and myosin light chain-2 gene expression in cultured ventricular myocytes by electrical stimulation of contraction. J Biol Chem 267:11665–11668.

    PubMed  CAS  Google Scholar 

  34. Kubisch C, Wollnik B, Maass A, Meyer R, Vetter H, Neyses L. 1993. Immediate-early gene induction by repetitive mechanical but not electrical activity in adult rat cardiomyocytes. FEBS Lett 335:37–40.

    Article  PubMed  CAS  Google Scholar 

  35. Johnson TB, Kent RL, Bubolz BA, McDermott PJ. 1994. Electrical stimulation of contractile activity accelerates growth of cultured neonatal cardiomyocytes. Circ Res 74:448–459.

    PubMed  CAS  Google Scholar 

  36. Williams HM, Ianuzzo CD. 1988. The effects of triiodothyronine on cultured rat cardiac myocytes. J Mol Cell Cardiol 20:689–699.

    Article  PubMed  CAS  Google Scholar 

  37. Nagai R, Zarain-Herzberg A, Brandl CJ, Fujii J, Tada M, MacLennan DH, Alpert NR, Periasamy M. 1989. Regulation of myocardial Ca2+ ATPase and phospholamban mRNA expression in response to pressure overload and thyroid hormone. Proc Natl Acad Sci USA 86:2966–2970.

    Article  PubMed  CAS  Google Scholar 

  38. Ito H, Hirata Y, Adachi S, Tanaka M, Tsujino M, Koike A, Nogami A, Marumo F, Hiroe M. 1993. Endothelin-1 is an autocrine/paracrine factor in the mechanism of angiotensin II-induced hypertrophy in cultured rat cardiomyocytes. J Clin Invest 92:398–403.

    Article  PubMed  CAS  Google Scholar 

  39. Sadoshima J-I, Xu Y, Slayter HS, 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 

  40. Dejonge HW, Van Heugten HAA, Lamers JMJ. 1995. Review: Signal transduction by the phosphatidylinositol cycle in myocardium. J Mol Cell Cardiol 27:93–106.

    Article  CAS  Google Scholar 

  41. Van Heugten HAA, Bezstarosti K, Dekkers DHW, Lamers JMJ. 1993. Homologous desensitization of the endothelin-1 receptor mediated phosphoinositide response in cultured neonatal rat cardiomyocytes. J Mol Cell Cardiol 25:41–52.

    Article  PubMed  Google Scholar 

  42. Dejonge HW, Van Heugten HAA, Bezstarosti K, Lamers JMJ. 1994. Distinct α1-adrenergic agonist- and endothelin-1-evoked phosphoinositol cycle responses in cultured neonatal rat cardiomyocytes. Biochem Biophys Res Commun 203:422–429.

    Article  CAS  Google Scholar 

  43. Bradford M. 1976. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–253.

    Article  PubMed  CAS  Google Scholar 

  44. Lee GM, Thornthwaite JT, Rasch EM. 1984. Picogram per cell determination of DNA by flow cytofluorometry. Anal Biochem 137:221–226.

    Article  PubMed  CAS  Google Scholar 

  45. Maniatis T, Fritsch EF, Sambrook J. 1982. Molecular Cloning, a Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.

    Google Scholar 

  46. Lamers JMJ, De Jonge-Stinis, Verdouw PD, Hulsmann WC. 1987. On the possible role of long-chain fatty acylcarnitine accumulation in producing functional and calcium permeability changes in membranes during myocardial ischaemia. Cardiovasc Res 21:313–322.

    Article  PubMed  CAS  Google Scholar 

  47. Schoutsen B, Blom JJ, Verdouw PD, Lamers. 1989. Calcium transport and phospholamban/ phosphorylation in sarcoplasmic reticulum of ischemic myocardium. J Mol Cell Cardiol 21:719–721.

    Article  PubMed  CAS  Google Scholar 

  48. Abdellatif MM, Neubauer CF, Lederer WJ, Rogers TB. 1991. Angiotensin-induced desensitization of the phosphoinositide pathway in cardiac cells occurs at the level of the receptor. Circ Res 69:800–809.

    PubMed  CAS  Google Scholar 

  49. Lamers JMJ, De Jonge HW, Panagia V, Van Heugten HA A. 1993. Receptor-mediated signalling through hydrolysis of membrane phospholipids in cardiomyocytes. Cardioscience 4:121–131.

    PubMed  CAS  Google Scholar 

  50. Kariya KI, Karns LR, Simpson PC. 1991. Expression of a constitutively activated mutant of the (β-isozyme of protein kinase C in cardiac myocytes stimulates the promotor of the β-myosin heavy chain. J Biol Chem 266:10023–10026.

    PubMed  CAS  Google Scholar 

  51. Shubeita HE, Martinson EA, Van Bilsen M, Chien KR, Brown JH. 1992. Transcriptional activation of the cardiac myosin light chain 2 and atrial natriuretic factor genes by protein kinase C in neonatal rat ventricular myocytes. Proc Natl Acad Sci USA 89:1305–1309.

    Article  PubMed  CAS  Google Scholar 

  52. Bogoyevitch MA, Parker PJ, Sugden PH. 1993. Characterization of protein kinase C isotype expression in adult rat heart. Protein kinase C-ε is a major isotype present, and it is activated by phorbol esters, epinephrine, and endothelin. Circ Res 72:757–767.

    PubMed  CAS  Google Scholar 

  53. Bogoyevitch MA, Glennon PE, Sugden PH. 1993. Endothelin-1, phorbol esters and phenylephrine stimulate MAP kinase activities in ventricular cardiomyocytes. FEBS Lett 317:271–275.

    Article  PubMed  CAS  Google Scholar 

  54. Dhalla NS, Das PK, Sharma GP. 1978. Subcellular basis of cardiac contractile failure. J Mol Cell Cardiol 10:363–385.

    Article  PubMed  CAS  Google Scholar 

  55. Schwartz LA, Sordahl LA, Entman ML, Allen IC, Reddy YS, Goldstein LA, Luchi RJ, Wyborny LE. 1973. Abnormal biochemistry in myocardial failure. Am J Cardiol 32: 407–422.

    Article  PubMed  CAS  Google Scholar 

  56. Lamers JMJ, Stinis JT. 1979. Defective calcium pump in the sarcoplamic reticulum of the hypertrophied rabbit heart. Life Sci 24:2313–2320.

    Article  PubMed  CAS  Google Scholar 

  57. Kojima M, Shiojima I, Yamazaki T, Komuro I, Yunzeng Z, Ying W, Mizuno T, Ueki K, Tobe K, Kadowaki T, Nagai R, Yazaki Y. 1994. Angiotensin II receptor antagonist TCV-116 induces regression of hypertensive left ventricular hypertrophy in vivo and inhibits the intracellular signalling pathway of stretch-mediated cardiomyocyte hypertrophy in vitro. Circulation 89:2204–2211.

    PubMed  CAS  Google Scholar 

  58. Ito H, Hiroe M, Hirata Y, Fujisaka H, Adachi S, Akimoto H, Ohta Y, Marumo F. 1994. Endothelin ETA receptor antagonist blocks cardiac hypertrophy provoked by hemodynamic overload. Circulation 89:2198–2203.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Han A. A. Van Heugten
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henriette W. De Jonge
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miriam A. Goedbloed
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karel Bezstarosti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hari S. Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pieter D. Verdouw
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jos M. J. Lamers
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. MRC Group in Experimental Cardiology Division of Cardiovascular Sciences St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, 351 Taché Avenue, Winnipeg, Manitoba, R2H 2A6, Canada

    Naranjan S. Dhalla (Distinguished Professor), Grant N. Pierce (Professor), Vincenzo Panagia (Professor) & Robert E. Beamish (Professor Emeritus) (Distinguished Professor),  (Professor),  (Professor) &  (Professor Emeritus)

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Kluwer Academic Publishers

About this chapter

Cite this chapter

Van Heugten, H.A.A. et al. (1995). Intracellular Signaling and Genetic Reprogramming During Development of Hypertrophy in Cultured Cardiomyocytes. In: Dhalla, N.S., Pierce, G.N., Panagia, V., Beamish, R.E. (eds) Heart Hypertrophy and Failure. Developments in Cardiovascular Medicine, vol 169. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1237-6_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-1237-6_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-8526-7

  • Online ISBN: 978-1-4613-1237-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation