Skip to main content
SpringerLink
Log in

Introduction to Molecular Medicine: A Contemporary View of Heart Failure

  • Chapter
Molecular Cardiology in Clinical Practice

Part of the book series: Basic Science for the Cardiologist ((BASC,volume 2))

  • 88 Accesses

Abstract

Molecular medicine is the application of the principles of molecular biology to the theory and practice of medicine. Although it is most modern, its evolution can be viewed in the larger context of the development of scientific medicine and its quest for the fundamental explanation of disease.

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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Huxley AF NR. Structural changes in muscle during contraction. Nature. 1954:971–973.

    Google Scholar 

  2. Huxley HE HJ. Changes in the cross-striations of muscle during contraction and stretch and their functional interpretation. Nature. 1954; 173:973–976.

    Article  PubMed  CAS  Google Scholar 

  3. Patterson SW PH, Starling HE. The regulation of the heart beat. J Physiol. 1914;48:465–513.

    PubMed  CAS  Google Scholar 

  4. Pauling L. Sickle ell anemia, a molecular disease. Science. 1949;110:543–548.

    Article  PubMed  CAS  Google Scholar 

  5. Anversa P, Ricci R, Olivetti G. Quantitative structural analysis of the myocardium during physiologic growth and induced cardiac hypertrophy: a review. J Am Coll Cardiol. 1986;7:1140–9.

    Article  PubMed  CAS  Google Scholar 

  6. Pauling L CR, Branson HR. The structure of proteins: two hydrogen-bonded helical configurations of the polypeptide chain. Proc Nat Acad Sci USA. 1951;37:205–211.

    Article  PubMed  CAS  Google Scholar 

  7. Pauling L CR. Configuration of polypeptide chains with favored orientations around single bonds: two new pleated sheets. Proc Nat Acad Sci USA. 1951;37:729–740.

    Article  PubMed  CAS  Google Scholar 

  8. Anfinsen CB. Principles that govern the folding of protein chains. Science. 1973; 181:223–30.

    Article  PubMed  CAS  Google Scholar 

  9. Colucci WS. Molecular and cellular mechanisms of myocardial failure. Am J Cardiol. 1997;80:15L–25L.

    Article  PubMed  CAS  Google Scholar 

  10. .Mittmann C ET, Scholz H. Cellular and molecular aspects of contractile dysfunction in heart failure. Cardiovascular Research. 1998;39:267–275.

    Article  PubMed  CAS  Google Scholar 

  11. Bristow M. Why does the myocardium fail? Insights from basic science. Lancet. 1998;352:8–14.

    Article  CAS  Google Scholar 

  12. Taeschler M BR. Some properties of contractile protein of the heart as studied on the extracted heart muscle preparation. Circulation Res. 1953;1:129–134.

    PubMed  CAS  Google Scholar 

  13. Elzinga M, Collins JH, Kuehl WM, Adelstein RS. Complete amino-acid sequence of actin of rabbit skeletal muscle. Proc Natl Acad Sci USA. 1973;70:2687–91.

    Article  PubMed  CAS  Google Scholar 

  14. Holmes KC, Popp D, Gebhard W, Kabsch W. Atomic model of the actin filament [see comments]. Nature. 1990;347:44–9.

    Article  PubMed  CAS  Google Scholar 

  15. Svent-Gyorgyi A. Contraction in the heart muscle fibre. Bull NY Acad Med. 1952;28:3–10.

    Google Scholar 

  16. Gordon AM HA, Julian FT. The variations in isometric tension with sarcomere length in vertebrate muscle fibers. JPhysiol. 1966; 184:170–192.

    CAS  Google Scholar 

  17. Dominguez R, Freyzon Y, Trybus KM, Cohen C. Crystal structure of a vertebrate smooth muscle myosin motor domain and its complex with the essential light chain: visualization of the pre-power stroke state. Cell. 1998;94:559–71.

    Article  PubMed  CAS  Google Scholar 

  18. Winkelmann DA, Mekeel H, Rayment I. Packing analysis of crystalline myosin subfragment-1. Implications for the size and shape of the myosin head. J Mol Biol. 1985; 181:487–501.

    Article  PubMed  CAS  Google Scholar 

  19. Tokunaga M, Sutoh K, Toyoshima C, Wakabayashi T. Location of the ATPase site of myosin determined by three-dimensional electron microscopy [published erratum appears in Nature 1987 Nov 26-Dec 2;330(6146):404]. Nature. 1987;329:635–8.

    Article  PubMed  CAS  Google Scholar 

  20. Yamamoto K. Binding manner of actin to the lysine-rich sequence of myosin subfragment 1 in the presence and absence of ATP. Biochemistry. 1989;28:5573–7.

    Article  PubMed  CAS  Google Scholar 

  21. Botts J, Thomason JF, Morales MF. On the origin and transmission of force in actomyosin subfragment 1. Proc Natl Acad Sci U S A. 1989;86:2204–8.

    Article  PubMed  CAS  Google Scholar 

  22. Gulick AM, Rayment I. Structural studies on myosin II: communication between distant protein domains. Bioessays. 1997;19:561–9.

    Article  PubMed  CAS  Google Scholar 

  23. Fisher AJ, Smith CA, Thoden J, Smith R, Sutoh K, Holden HM, Rayment I. Structural studies of myosin:nucleotide complexes: a revised model for the molecular basis of muscle contraction. Biophys J. 1995;68:19S–26S; discussion 27S-28S.

    PubMed  CAS  Google Scholar 

  24. Rayment I, Holden HM, Whittaker M, Yohn CB, Lorenz M, Holmes KC, Milligan RA. Structure of the actin-myosin complex and its implications for muscle contraction [see comments]. Science. 1993;261:58–65.

    Article  PubMed  CAS  Google Scholar 

  25. Beadle GW, Tatum, E.L. Genetic control of biochemical reactions in Neurospora. Proc Natl Acad Sci. 1941;27:499–506.

    Article  PubMed  CAS  Google Scholar 

  26. Watson JD, Crick, F.H.C. A structure for deoxyribonucleic acid. Nature. 1953;171:737–738.

    Article  PubMed  CAS  Google Scholar 

  27. Towbin JA. Molecular genetic aspects of cardiomyopathy. Biochemical Medicine and Metabolic Biology. 1993;49:285–320.

    Article  PubMed  CAS  Google Scholar 

  28. Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, Seidman JG. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell. 1990;62:999–1006.

    Article  PubMed  CAS  Google Scholar 

  29. Vikstrom KL, Leinwand LA. Contractile protein mutations and heart disease. Curr Opin Cell Biol. 1996;8:97–105.

    Article  PubMed  CAS  Google Scholar 

  30. Watkins H, Rosenzweig A, Hwang DS, Levi T, McKenna W, Seidman CE, Seidman JG. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy [see comments]. N Engl J Med. 1992;326:1108–14.

    Article  PubMed  CAS  Google Scholar 

  31. Rayment I, Holden HM, Sellers JR, Fananapazir L, Epstein ND. Structural interpretation of the mutations in the beta-cardiac myosin that have been implicated in familial hypertrophic cardiomyopathy. Proc Natl Acad Sci USA. 1995;92:3864–8.

    Article  PubMed  CAS  Google Scholar 

  32. McKenna WJ, Coccolo F, Elliott PM. Genes and disease expression in hypertrophic cardiomyopathy [In Process Citation]. Lancet. 1998;352:1162–3.

    Article  PubMed  CAS  Google Scholar 

  33. Olson TM, Michels VV, Thibodeau SN, Tai YS, Keating MT. Actin mutations in dilated cardiomyopathy, a heritable form of heart failure. Science. 1998;280:750–2.

    Article  PubMed  CAS  Google Scholar 

  34. Ortiz-Lopez R, Li H, Su J, Goytia V, Towbin JA. Evidence for a dystrophin missense mutation as a cause of X-linked dilated cardiomyopathy [see comments]. Circulation. 1997;95:2434–40.

    PubMed  CAS  Google Scholar 

  35. Spyrou N, Philpot J, Foale R, Camici PG, Muntoni F. Evidence of left ventricular dysfunction in children with merosin-deficient congenital muscular dystrophy. Am Heart J. 1998;136:474–6.

    Article  PubMed  CAS  Google Scholar 

  36. Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med. 1998;339:900–5.

    Article  PubMed  CAS  Google Scholar 

  37. Abbott BC, Wilke, D.R. The relation between velocity of shortening and the tension-length curve of skeletal muscle. J Physiol. 1953;120:214–223.

    PubMed  CAS  Google Scholar 

  38. Abbott BC, Mommaerts, W.F.H.M. A study of inotropic mechanisms in the papillary muscle preparation. J Gen Physiol. 1959;42:533–551.

    Article  PubMed  CAS  Google Scholar 

  39. Alpert NR, Mulieri LA, Litten RZ. Functional significance of altered myosin adenosine triphosphatase activity in enlarged hearts. Am J Cardiol. 1979;44:946–53.

    PubMed  CAS  Google Scholar 

  40. Barany M, Conover TE, Schliselfeld LH, Gaetjens E, Goffart M. Relation of properties of isolated myosin to those of intact muscles of the cat and sloth. Eur J Biochem. 1967;2:156–64.

    Article  PubMed  CAS  Google Scholar 

  41. Nadal-Ginard B, Mahdavi V. Molecular basis of cardiac performance. Plasticity of the myocardium generated through protein isoform switches. J Clin Invest. 1989;84:1693–700.

    Article  PubMed  CAS  Google Scholar 

  42. Saez LJ, Gianola KM, McNally EM, Feghali R, Eddy R, Shows TB, Leinwand LA. Human cardiac myosin heavy chain genes and their linkage in the genome. Nucleic Acids Res. 1987;15:5443–59.

    Article  PubMed  CAS  Google Scholar 

  43. Kurabayashi M, Tsuchimochi H, Komuro I, Takaku F, Yazaki Y. Molecular cloning and characterization of human cardiac alpha-and beta-form myosin heavy chain complementary DNA clones. Regulation of expression during development and pressure overload in human atrium. J Clin Invest. 1988;82:524–31.

    PubMed  CAS  Google Scholar 

  44. Nakao K, Minobe W, Roden R, Bristow MR, Leinwand LA. Myosin heavy chain gene expression in human heart failure. J Clin Invest. 1997;100:2362–70.

    PubMed  CAS  Google Scholar 

  45. Katz AM. Cardiomyopathy of overload. A major determinant of prognosis in congestive heart failure [see comments]. N Engl J Med. 1990;322:100–10.

    Article  PubMed  CAS  Google Scholar 

  46. Jacob F, Monod, J. Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol. 1961;3:318–356.

    Article  PubMed  CAS  Google Scholar 

  47. Hefti MA, Harder BA, Eppenberger HM, Schaub MC. Signaling pathways in cardiac myocyte hypertrophy. J Mol Cell Cardiol. 1997;29:2873–92.

    Article  PubMed  CAS  Google Scholar 

  48. Anversa P, Olivetti G, Melissari M, Loud AV. Stereological measurement of cellular and subcellular hypertrophy and hyperplasia in the papillary muscle of adult rat. J Mol Cell Cardiol. 1980;12:781–95.

    Article  PubMed  CAS  Google Scholar 

  49. Bristow MR, Gilbert, E.M., Lowes, B.D., Minobe WA, Shakar, S.F., Quaife, R.A., Abraham, W.T. Changes in gene expression asociated with b-blocker-related improvements in ventricular systolic function. Circulation. 1997;96:I–92.

    Google Scholar 

  50. Cheng W, Li B, Kajstura J, Li P, Wolin MS, Sonnenblick EH, Hintze TH, Olivetti G, Anversa P. Stretch-induced programmed myocyte cell death. J Clin Invest. 1995;96:2247–59.

    PubMed  CAS  Google Scholar 

  51. Teiger E, Than VD, Richard L, Wisnewsky C, Tea BS, Gaboury L, Tremblay J, Schwartz K, Hamet P. Apoptosis in pressure overload-induced heart hypertrophy in the rat. J Clin Invest. 1996;97:2891–7.

    PubMed  CAS  Google Scholar 

  52. Glennon PE, Kaddoura S, Sale EM, Sale GJ, Fuller SJ, Sugden PH. Depletion of mitogen-activated protein kinase using an antisense oligodeoxynucleotide approach downregulates the phenylephrine-induced hypertrophic response in rat cardiac myocytes. Circ Res. 1996;78:954–61.

    PubMed  CAS  Google Scholar 

  53. Sadoshima J, Jahn L, Takahashi T, Kulik TJ, Izumo S. Molecular characterization of the stretch-induced adaptation of cultured cardiac cells. An in vitro model of load-induced cardiac hypertrophy. J BiolChem. 1992;267:10551–60.

    CAS  Google Scholar 

  54. Kudoh S, Komuro I, Hiroi Y, Zou Y, Harada K, Sugaya T, Takekoshi N, Murakami K, Kadowaki T, Yazaki Y. Mechanical stretch induces hypertrophie responses in cardiac myocytes of angiotensin II type la receptor knockout mice. J Biol Chem. 1998;273:24037–43.

    Article  PubMed  CAS  Google Scholar 

  55. Wollert KC, Taga T, Saito M, Narazaki M, Kishimoto T, Glembotski CC, Vernallis AB, Heath JK, Pennica D, Wood WI, Chien KR. Cardiotrophin-1 activates a distinct form of cardiac muscle cell hypertrophy. Assembly of sarcomeric units in series VIA gpl30/leukemia inhibitory factor receptor-dependent pathways. J Biol Chem. 1996;271:9535–45.

    Article  PubMed  CAS  Google Scholar 

  56. Heinrich PC, Behrmann I, G Ml-N, Schaper F, Graeve L. Interleukin-6-type cytokine signalling through the gpl30/Jak/STAT pathwayl. Biochem J. 1998;334:297–314.

    PubMed  CAS  Google Scholar 

  57. Calderone A, Takahashi N, Izzo NJ, Jr., Thaik CM, Colucci WS. Pressure-and volume-induced left ventricular hypertrophies are associated with distinct myocyte phenotypes and differential induction of peptide growth factor mRNAs. Circulation. 1995;92:2385–90.

    PubMed  CAS  Google Scholar 

  58. Erdmann J, Hassfeld S, Kaliisch H, Fleck E, Regitz-Zagrosek V. Cloning and characterization of the 5’-flanking region of the human cardiotrophin-1 gene. Biochem Biophys Res Commun. 1998;244:494–7.

    Article  PubMed  CAS  Google Scholar 

  59. .Narula J, Haider N, Virmani R, DiSalvo TG, Kolodgie FD, Hajjar RJ, Schmidt U, Semigran MJ, Dec GW, Khaw BA. Apoptosis in myocytes in end-stage heart failure [see comments]. N Engl J Med. 1996;335:1182–9.

    Article  PubMed  CAS  Google Scholar 

  60. Dec GW, Fuster V. Idiopathic dilated cardiomyopathy [see comments]. N Engl J Med. 1994;331:1564–75.

    Article  PubMed  CAS  Google Scholar 

  61. Olivetti G, Abbi R, Quaini F, Kajstura J, Cheng W, Nitahara JA, Quaini E, Di Loreto C, Beltrami CA, Krajewski S, Reed JC, Anversa P. Apoptosis in the failing human heart. N Engl J Med. 1997;336:1131–41.

    Article  PubMed  CAS  Google Scholar 

  62. Chandrasekar B, Melby PC, Pennica D, Freeman GL. Overexpression of cardiotrophin-1 and gpl30 during experimental acute Chagasic cardiomyopathy. Immunol Lett. 1998;61:89–95.

    Article  PubMed  CAS  Google Scholar 

  63. Barbara G, Di Lorenzo G, Grisorio B, Barbarini G. Incidence of Dilated Cardiomyopathy and Detection of HIV in Myocardial Cells of HIV-Positive Patients. N Engl J Med. 1998;339:1093–1099.

    Article  Google Scholar 

  64. Garner I, Sassoon D, Vandekerckhove J, Alonso S, Buckingham ME. A developmental study of the abnormal expression of alpha-cardiac and alpha-skeletal actins in the striated muscle of a mutant mouse. Dev Biol. 1989; 134:236–45.

    Article  PubMed  CAS  Google Scholar 

  65. Buckingham ME. Actin and myosin multigene families: their expression during the formation of skeletal muscle. Essays Biochem. 1985;20:77–109.

    PubMed  CAS  Google Scholar 

  66. Katz AM. The cardiomyopathy of overload: an unnatural growth response in the hypertrophied heart. Ann Intern Med. 1994;121:363–71.

    PubMed  CAS  Google Scholar 

  67. Takahashi T, Allen PD, Izumo S. Expression of A-, B-, and C-type natriuretic peptide genes in failing and developing human ventricles. Correlation with expression of the Ca(2+)-ATPase gene. Circ Res. 1992;71:9–17.

    PubMed  CAS  Google Scholar 

  68. Cornelius T, Holmer SR, Müller FU, Riegger GA, Schunkert H. Regulation of the rat atrial natriuretic peptide gene after acute imposition of left ventricular pressure overload. Hypertension. 1997;30:1348–55.

    PubMed  CAS  Google Scholar 

  69. Sack MN, Disch DL, Rockman HA, Kelly DP. A role for Sp and nuclear receptor transcription factors in a cardiac hypertrophie growth program. Proc Natl Acad Sci USA. 1997;94:6438–43.

    Article  PubMed  CAS  Google Scholar 

  70. Yue P, Long CS, Austin R, Chang KC, Simpson PC, Massie BM. Post-infarction heart failure in the rat is associated with distinct alterations in cardiac myocyte molecular phenotype [In Process Citation]. J Mol Cell Cardiol. 1998;30:1615–30.

    Article  PubMed  CAS  Google Scholar 

  71. Boxer LM, Miwa T, Gustafson TA, Kedes L. Identification and characterization of a factor that binds to two human sarcomeric actin promoters. J Biol Chem. 1989;264:1284–92.

    PubMed  CAS  Google Scholar 

  72. Navankasattusas S, Sawadogo M, van Bilsen M, Dang CV, Chien KR. The basic helix-loop-helix protein upstream stimulating factor regulates the cardiac ventricular myosin light-chain 2 gene via independent cis regulatory elements. Mol Cell Biol. 1994; 14:7331–9.

    PubMed  CAS  Google Scholar 

  73. Hasegawa K, Lee SJ, Jobe SM, Markham BE, Kitsis RN. cis-Acting sequences that mediate induction of beta-myosin heavy chain gene expression during left ventricular hypertrophy due to aortic constriction [see comments]. Circulation. 1997;96:3943–53.

    PubMed  CAS  Google Scholar 

  74. Molkentin JD, Lu JR, Antos CL, Markham B, Richardson J, Robbins J, Grant SR, Olson EN. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell. 1998;93:215–28.

    Article  PubMed  CAS  Google Scholar 

  75. Zilberman A, Dave V, Miano J, Olson EN, Periasamy M. Evolutionarily conserved promoter region containing CArG*-like elements is crucial for smooth muscle myosin heavy chain gene expression. Circ Res. 1998;82:566–75.

    PubMed  CAS  Google Scholar 

  76. Schiaffino S, Samuel JL, Sassoon D, Lompre AM, Garner I, Marotte F, Buckingham M, Rappaport L, Schwartz K. Nonsynchronous accumulation of alpha-skeletal actin and beta-myosin heavy chain mRNAs during early stages of pressure-overload-induced cardiac hypertrophy demonstrated by in situ hybridization. Circ Res. 1989;64:937–48.

    PubMed  CAS  Google Scholar 

  77. Xiao Q, Ojamaa K. Regulation of cardiac alpha-myosin heavy chain gene transcription by a contractile-responsive E-box binding protein. J Mol Cell Cardiol. 1998;30:87–95.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Robert Wood Johnson School of Medicine, University of Medicine and Dentistry of N.J., USA

    Michael R. Sanders M.D.

Authors
  1. Michael R. Sanders M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Medicine, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, USA

    Michael Sanders  & John B. Kostis  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Kluwer Academic Publishers

About this chapter

Cite this chapter

Sanders, M.R. (1999). Introduction to Molecular Medicine: A Contemporary View of Heart Failure. In: Sanders, M., Kostis, J.B. (eds) Molecular Cardiology in Clinical Practice. Basic Science for the Cardiologist, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-0-585-38141-1_1

Download citation

  • DOI: https://doi.org/10.1007/978-0-585-38141-1_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-7923-8602-5

  • Online ISBN: 978-0-585-38141-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation