Skip to main content

Sympathetic modulation of the cardiac myocyte phenotype: studies with a cell-culture model of myocardial hypertrophy

  • Conference paper
Cardiac Adaptation in Heart Failure

Summary

Myocardial hypertrophy is the common endpoint of many cardiovascular stimuli such as hypertension, myocardial infarction, valvular disease, and congestive failure. Catecholamines have long been implicated in the pathogenesis of myocardial hypertrophy, however, it is very difficult to sort out catecholamine mechanisms in vivo. We have developed a cell-culture model which excludes hemodynamic effects and allows the assignment of receptor specificity to catecholamine effects. Utilizing this system, we have shown that stimulation of the α1 adrenergic receptor leads to the development of myocardial hypertrophy and results in the selective up-regulation of the fetal/neonatal mRNAs encoding skeletal α-actin and β-MHC, a pattern similar to that seen with hypertrophy in-vivo. Utilizing a co-transfection assay, we have also obtained data that suggest that the β-PKC isozyme is in a pathway regulating transcription of the β-MHC isogene. β adrenergic stimulation of the cultured cardiac myocytes also results in a modest degree of hypertrophy, however, this effect may be dependent upon myocyte contractile activity and may involve, at least in part, the non-muscle cells present in the culture system.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight 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. Barka T, van der Noen H, Shaw PA (1987) Proto-oncogene fos (c-fos) expression in the heart. Oncogene 1:439–443

    PubMed  CAS  Google Scholar 

  2. Bevan JA (1978) Norepinephrine and the presynaptic control of adrenergic transmitter release. Fed Proc 39:187–190

    Google Scholar 

  3. Bishop JM (1985) Viral oncogenes. Cell 42:23–38

    Article  PubMed  CAS  Google Scholar 

  4. Bishopric NH, Simpson PC, Ordahl CP (1987) Induction of the skeletal α-actin gene in α1-adrenoceptor-mediated hypertrophy of rat cardiac myocytes. J Clin Invest 80:1194–1199

    Article  PubMed  CAS  Google Scholar 

  5. Casale PN, Devereux R, Milner M, Zullo G, Harshfield GA, Pickering TG, Laragh JH (1986) Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Int Med 105:173–178

    PubMed  CAS  Google Scholar 

  6. Casscells W, Speir E, Sasse J, Klagsburn M, Allen P, Lee M, Calvo B, Chiba M, Haggroth L, Folkman J, Epstein SE (1990) Isolation, characterization, and localization of heparinbinding growth factors in the heart. J Clin Invest 85:433–441

    Article  PubMed  CAS  Google Scholar 

  7. Casscells W, Speir EH, Bazoberry F, Yu Z-X, Chiba M, Thompson N, Flanders K, Sporn M, Ferrans VJ (1989) Transforming growth factor beta-1 in normal heart and myocardial infarction (abstract). Circulation 80:11–452

    Google Scholar 

  8. Cercek B, Fishbein MC, Forrestor JS, Heifant RH, Fagin JA (1989) Induction of vascular insulin-like growth factor-1 mRNA after balloon denudation precedes neointimal proliferation (abstract). Circulation 80:11–453

    Google Scholar 

  9. Chiba M, Bazoberry F, Speir EH, Sasse J, Nesbitt CP, Baird A, Ferrans VJ, Epstein SE, Casscells W (1989) Role of basic fibroblast growth factor in angiogenesis, healing, and hypertrophy after rat myocardial infarction (abstract). Circulation 80:II-452

    Google Scholar 

  10. Clegg CH, Linkhart TA, Olwin BB, Hauschka SD (1987) Growth factor control of skeletal muscle differentiation:commitment to terminal differentiation occurs in Gl phase and is repressed by fibroblast growth factor. J Cell Biol 105:949–956

    Article  PubMed  CAS  Google Scholar 

  11. Corea L, Bentivoglio M, Verdecchia P, Motolese M (1984) Plasma norepinephrine and left ventricular hypertrophy in systematic hypertension. Am J Cardiol 53: 1299–1303

    Article  PubMed  CAS  Google Scholar 

  12. Darnell JE (1982) Variety in the level of gene control in eukaryotic cells. Nature 297:365–371

    Article  PubMed  CAS  Google Scholar 

  13. de Champlain J, Farley L, Cousineau D, van Ameringen M-R (1976) Circulating catecholamine levels in human and experimental hypertension. Circ Res 38:109–114

    PubMed  Google Scholar 

  14. Eghbali M (1989) Cellular origin and distribution of transforming growth factor-β 1 in the normal rat myocardium. Cell Tissue Res 256:553–558

    Article  PubMed  CAS  Google Scholar 

  15. Engelmann GL, Boehm KD, Haskell JF, Khairallah PA, Ilan J (1989) Insulin-like growth factors and neonatal cardiomyocyte development: ventricular gene expression and membrane receptor variations in normotensive and hypertensive rats. Mol Cell Endocrinol 63:1–14

    Article  PubMed  CAS  Google Scholar 

  16. Fuller SJ, Gaitanaki CJ, Sugden PH (1990) Effects of catecholamines on protein synthesis in cardiac myocytes and perfused hearts isolated from adult rats: stimulation of translation is mediated through the α1-adrenoceptor. Biochem J 266:727–736

    PubMed  CAS  Google Scholar 

  17. Furukawa Y, Furukawa S, Satoyoshi E (1984) Nerve growth factor secreted by mouse heart cells culture. J Biol Chem 259:1259–1264

    PubMed  CAS  Google Scholar 

  18. Genovese A, Chiariello M, Bozzaotre M, Latte S, DeAlfieri W, Condorelli M (1984) Adrenergic activity as a modulating factor in the genesis of myocardial hypertrophy in the rat. Exp Mol Pathol 41:390–396

    Article  PubMed  CAS  Google Scholar 

  19. Heldin CH, Westermark B (1984) Growth factors: mechanism of action and relation to oncogenes. Cell 37:9–20

    Article  PubMed  CAS  Google Scholar 

  20. Henrich CJ, Simpson PC (1988) Differential acute and chronic response of protein kinase C in cultured neonatal rat heart myocytes of α1-adrenergic and phorbol ester stimulation. J Mol Cell Cardiol 20:1081–1085

    Article  PubMed  CAS  Google Scholar 

  21. Izumo S, Lompre AM, Matsuoka R, Koren G, Schwartz K, Nadal-Ginard B, Mahdavi V (1987) Myosin heavy chain messenger RNA and protein isoform transitions during cardiac hypertrophy: Interaction between hemodynamic and thyroid hormone-induced signals. J Clin Invest 79:970–977

    Article  PubMed  CAS  Google Scholar 

  22. Kardami E, Fandrich RR (1989) Basic fibroblast growth factor in atria and ventricles of the vertebrate heart. J Cell Biol 109:1865–1875

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  24. Karliner JS, Kagiya T, Simpson PC (1990) Effects of pertussis toxin on α1-agonist-mediated phosphatidylinositide turnover and myocardial cell hypertrophy in neonatal rat ventricular myocytes. Experientia 46:81–84

    Article  PubMed  CAS  Google Scholar 

  25. King BD, Sack D, Kichuk MR, Hintze TH (1987) Absence of hypertension despite chronic marked elevations in plasma norepinephrine in conscious dogs. Hypertension 9:582–590

    PubMed  CAS  Google Scholar 

  26. Kohtz D, Disehe N, Inagami T, Goldman B (1989) Growth and partial differentiation of presumptive human cardiac myoblasts in culture. J Cell Biol 108:1067–1078

    Article  PubMed  CAS  Google Scholar 

  27. Lake CR (1984) Essential hypertension: are catecholamines involved? Fed Proc 43:45–46

    PubMed  CAS  Google Scholar 

  28. Laks M, Morady F, Swan H (1969) Myocardial hypertrophy produced by chronic infusion of subhypertensive doses of norepinephrine in the dog. Chest 64:75–78

    Article  Google Scholar 

  29. Laks MM, Morady F (1976) Norepinephrine-the myocardial hypertrophy hormone? Am Heart J. 91:674–675

    Article  PubMed  CAS  Google Scholar 

  30. Lee HR, Henderson SA, Reynolds R, Dunnmon P, Yuan D, Chien KR (1988) α1-adrenergic stimulation of cardiac gene transcription in neonatal rat myocardial cells: effects on myosin light chain-2 gene expression. J Biol Chem 263:7352–7358

    PubMed  CAS  Google Scholar 

  31. Leenen FHH, Smith DL, Farkas RM, Reeves RA, Marquez-Julio A (1987) Vasodilators and regression of left ventricular hypertrophy: hydralazine versus prazosin in hypertensive human. Am J Med 82:969–978

    Article  PubMed  CAS  Google Scholar 

  32. Long CS, Henrich CJ, Simpson PC (1991) A growth factor for cardiac myocytes is produced by cardiac nonmyocytes. Cell Reg 2:1081–1095

    CAS  Google Scholar 

  33. Long CS, Ordahl CP, Simpson PC (1989) α1-Adrenergic receptor stimulation of sarcomeric actin isogene transcription in hypertrophy of cultured rat heart muscle cells. J Clin Invest 83:1078–1082

    Article  PubMed  CAS  Google Scholar 

  34. Marino TA, Walter RA, D’Ambra K, Mercer WE (1989) Effects of catecholamines on fetal rat cardiocytes in vitro. Am J Anat 186:127–132

    Article  PubMed  CAS  Google Scholar 

  35. Massague’ J, Cheifetz S, Endo T, Nadal-Ginard B (1986) Type β transforming growth factor is an inhibitor of myogenic differentiation. Proc Natl Acad Sci USA 83:8206–8210

    Article  Google Scholar 

  36. 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 

  37. Mochly-Rosen D, Henrich CJ, Cheever L, Khaner H, Simpson PC (1990) A protein kinase C isozyme is translocated to cytoskeletal elements on activation. Cell Regul 1:693–706

    PubMed  CAS  Google Scholar 

  38. Norrgren G, Ebendal T (1986) Nerve growth factor in medium conditioned by embryonic chicken heart cells. Int J Develop Neuroscience 4:41–49

    Article  CAS  Google Scholar 

  39. Ostman-Smith I (1981) Cardiac sympathetic nerves as the final common pathway in the induction of adaptive cardiac hypertrophy. Clin Sci 61:265–272

    PubMed  CAS  Google Scholar 

  40. Parket TG, Schneider MD (1990) Peptide growth factors can provoke “fetal” contractile protein gene expression in rat cardiac myocytes. J Clin Invest 85:507–514

    Article  Google Scholar 

  41. Pfeffer JM, Pfeffer MA, Mirsky I, Braunwald E (1982) Regression of left ventricular hypertrophy and prevention of left ventricular dysfunction by Captopril in the spontaneously hypertensive rat. Proc Natl Acad Sci USA 79:3310–3314

    Article  PubMed  CAS  Google Scholar 

  42. Pfeffer MA, Pfeffer JM (1990) Reversing cardiac hypertrophy in hypertension. N Engl J Med 322:1388–1390

    Article  PubMed  CAS  Google Scholar 

  43. Quinckler W, Pfeffer J (1989) Isolation of heparin binding growth factors from bovine, porcine, and canine hearts. Eur J Biochem 181:67–73

    Article  Google Scholar 

  44. Rossi MA, Carillo SV (1985) Does norepinephrine play a central causative role in the process of cardiac hypertrophy? Am Heart J 109:622–624

    Article  PubMed  CAS  Google Scholar 

  45. Sarzani R, Arnoldi G, Chobanian AV (1991) Hypertension-induced changes of platelet-derived growth factor receptor expression in rat aorta and heart. Hypertension 17:888–895

    PubMed  CAS  Google Scholar 

  46. Sasaki H, Hoshi H, Hong Y-M, Suzuki T, Kato T, Sasaki H, Saito M, Youki H, Karube K, Konno S, Onodera M, Saito T, Aoyagi S (1989) Purification of acidic fibroblast growth factor from bovine heart and its localization in the cardiac myocytes. J Biol Chem 264:17606–17612

    PubMed  CAS  Google Scholar 

  47. Scheuer J, Bahn AK (1979) Cardiac contractile proteins: adenosine triphosphatase activity and physiological function. Circ Res 45:1–12

    PubMed  CAS  Google Scholar 

  48. Schneider MD, Olson EN (1988) Control of myogenic differentiation by cellular oncogenes. Mol Neurobiol 2:1–39

    Article  PubMed  CAS  Google Scholar 

  49. Schneider MD, Payne PA, Ueno H, Perryman MB, Roberts R (1986) Dissociated expression of c-myc and a fos-related competence gene during cardiac myogenesis. Mol Cell Biol 6:4140–4143

    PubMed  CAS  Google Scholar 

  50. Schulman SP, Weiss JL, Becker LC, Gottlieb SO, Woodruff KM, Weisfeldt ML, Gerstenblith G (1990) The effects of antihypertensive therapy on left ventricular mass in elderly patients. N Engl J Med 322:1350–1356

    Article  PubMed  CAS  Google Scholar 

  51. Schwartz K, de la Bastie D, Bouveret P, Oliveiro P, Alonso S, Buckingham M (1986) α-skeletal muscle actin mRNAs accumulate in hypertrophied adult rat hearts. Circ Res 59:551–555

    PubMed  CAS  Google Scholar 

  52. Sharma HS, Kandolf R, Markert T, Schaper W (1989) Localization of endothelial cell growth factor-β (β-ECGF) mRNA in pig heart during collateralization (abstract). Circulation 80:11–453

    Google Scholar 

  53. Simpson P (1983) Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells in an alpha1-adrenergic response. J Clin Invest 72:732–738

    Article  PubMed  CAS  Google Scholar 

  54. Simpson P (1984) Calcium entry blockers inhibit catecholamine-induced beating but not catecholamine-stimulated hypertrophy of cultured rat heart cells (abstract). Clin Res 33:90A

    Google Scholar 

  55. 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 β 1-adrenergic receptor interaction: evidence for independent regulation of growth and beating. Circ Res 56:884–894

    PubMed  CAS  Google Scholar 

  56. Simpson P, McGrath A, Savion S (1982) Myocyte hypertrophy in neonatal rat heart cultures and its regulation by serum and by catecholamines. Circ Res 51:787–801

    PubMed  CAS  Google Scholar 

  57. Simpson P, Savion S (1982) Differentiation of rat myocytes in single cell cultures with and without proliferating nonmyocardial cells:cross-striations, ultrastructure, and chronotropic response to isoproterenol. Circ Res 50:101–116

    PubMed  CAS  Google Scholar 

  58. Simpson PC (1989) Proto-oncogenes and cardiac hypertrophy. Ann Rev Physiol 51:189–202

    Article  CAS  Google Scholar 

  59. Speir E, Yi-Fu Z, Lee M, Shrivastav S, Casscells W (1988) Fibroblast growth factors are present in adult cardiac myocytes, in vivo. Biochem Biophys Res Commun 157:1336–1340

    Article  CAS  Google Scholar 

  60. Stanton HC, Brenner G, Mayfield ED Jr. (1969) Studies on isoproterenol-induced cardiomegaly in rats. Am Heart J 77:72–80

    Article  PubMed  CAS  Google Scholar 

  61. Starksen NF, Simpson PC, Bishopric N, Coughlin SR, Lee WMF, Escobedo JA, Williams LT (1986) Cardiac myocyte hypertrophy is associated with c-myc proto-oncogene expression. Proc Natl Acad Sci USA 83:8348–8350

    Article  PubMed  CAS  Google Scholar 

  62. Strauer BE, Bayer F, Brecht HM, Motz W (1985) The influence of sympathetic nervous activity on regression of cardiac hypertrophy. J Hypertension 3 (Suppl 4):S39–S44

    CAS  Google Scholar 

  63. Sugishita Y, Iida K, Yukisada K, Ito I (1990) Cardiac determinants of regression of left ventricular hypertrophy in essential hypertension with antihypertensive treatment. J Am Coll Cardiol 15:665–671

    Article  PubMed  CAS  Google Scholar 

  64. Tarazi RC, Sen S, Saragoca M, Khairallah P (1982) The multifactorial role of catecholamines in hypertensive cardiac hypertrophy. Eur Heart J 3 (Suppl A): 103–110

    PubMed  CAS  Google Scholar 

  65. Trimarco B, Ricciardelli B, De Luca N, De Simone A, Cuocolo A, Galva MD, Picotti GB, Condorelli M (1985) Participation of endogeneous catecholamines in the regulation of left ventricular mass in progeny of hypertensive parents. Circulation 72:38–46

    Article  PubMed  CAS  Google Scholar 

  66. Waspe LE, Ordahl CP, Simpson PC (1990) The cardiac β-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 

  67. Weiner HL, Swain JL (1989) Acidic fibroblast growth factor mRNA is expressed by cardiac myocytes in culture and the protein is localized to the extracellular matrix. Proc Natl Acad Sci USA 86:2683–2687

    Article  PubMed  CAS  Google Scholar 

  68. Wunsch M, Sharma HS, Bernotat-Danielowski S, Schott RJ, Schaper J, Bleese N, Schaper W (1989) Expression of transforming growth factor β 1 (TGFβ 1) in collateralized swine heart (abstract). Circulation 80:11–453

    Google Scholar 

  69. Zierhut W, Zimmer H-G (1989) Significance of myocardial α- and β-adrenoceptors in catecholamine-induced cardiac hypertrophy. Circ Res 65:1417–1425

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1992 Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt

About this paper

Cite this paper

Long, C.S., Kariya, K., Karns, L., Simpson, P.C. (1992). Sympathetic modulation of the cardiac myocyte phenotype: studies with a cell-culture model of myocardial hypertrophy. In: Holtz, J., Drexler, H., Just, H. (eds) Cardiac Adaptation in Heart Failure. Steinkopff. https://doi.org/10.1007/978-3-642-72477-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-72477-0_3

  • Publisher Name: Steinkopff

  • Print ISBN: 978-3-642-72479-4

  • Online ISBN: 978-3-642-72477-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics