Skip Navigation

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Chien, K.R.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Chien, K.R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


Genomic circuits and the integrative biology of cardiomyopathies

K.R. Chien*

UCSD-Salk Program in Molecular Medicine and the UCSD Institute of Molecular Medicine, La Jolla, California, U.S.A.

* Correspondence: Kenneth R. Chien, MD, PhD, UCSD School of Medicine, 0613-C, La Jolla, California 92093, U.S.A.

Abstract

A growing body of clinical and experimental evidence has led to the identification of nodal points in the pathways that drive the onset and progression of human cardiomyopathies. Studies of familial forms of human cardiomyopathy have documented that there are links between sarcomeric and cytoskeletal components, and onset of hypertrophic and dilated cardio-myopathy, respectively. Studies of gene-targeted mice suggest that pathways that guide biomechanical signalling, myocyte survival, cardiac calcium cycling and the electrophysiological function of conduction system lineages may play critical roles in the onset of distinct phenotypes that arise in human forms of cardiomyopathy. The present brief review highlights a few of these recent advances and provides a perspective for future clinical and experimental studies.

Key Words: Networks • conserved • cardiac-specific genes • genomic databases • integrated genomic circuits

References

  1. Seidman CE, Seidman JG. Molecular genetics of inherited cardiomyopathies. Chien KR, Breslow J, Leiden J, Rosenberg R, Seidman CE. Molecular Basis of Cardiovascular Disease (Companion text to E. Braunwald's Heart Disease). Cambridge, MA: W.B. Saunders Co; 1999. p. 251–263
  2. Chen J, Chien KR. Complexity in simplicity: monogenic disorders and complex cardiomyopathies. J Clin Invest. 1999;103:1483–1485[Web of Science][Medline]
  3. Arber S, Hunter JJ, Ross J Jr, et al. MLP-deficient mice exhibit a disruption of cardiac myofibrillar organization, dilated cardiomyopathy, and heart failure. Cell. 1997;88:393–403[CrossRef][Web of Science][Medline]
  4. Pasmforoush M, Pomiès P, Peterson KL, et al. Adult mice deficient in actinin-associated LIM-domain protein reveal a developmental pathway for right ventricular cardiomyopathy. Nat Med. 2001;7:591–597[CrossRef][Web of Science][Medline]
  5. Chien KR. Stress pathways and heart failure. Cell. 1999;98:555–558[CrossRef][Web of Science][Medline]
  6. Chen J, Kubalak SW, Chien KR. Ventricular muscle restricted gene targeting of the RXR{alpha} gene reveals a non-cell autonomous requirement in cardiac chamber morphogenesis. Development. 1998;125:1943–1949[Abstract]
  7. Chien KR. Genomic circuits and the integrative biology of cardiac diseases. Nature. 2000;407:227–232[CrossRef][Medline]
  8. Hirota H, Chen Ju, Betz UAK, et al. Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress. Cell. 1999;97:189–198[CrossRef][Web of Science][Medline]
  9. Pennica D, Chien KR. Cardiotrophin-1: a multifunctional cytokine that signals via LIF-receptor-gp130 dependent pathways. Cytokine Growth Factor Rev. 1996;7:81–91[CrossRef][Medline]
  10. Zhao YY, Sawyer DR, Baliga RR, et al. Neuregulins promote survival and growth of cardiac myocytes. Persistence of ErbB2 and ErbB4 expression in neonatal and adult ventricular myocytes. J Biol Chem. 1998;273:10261–10269[Abstract/Free Full Text]
  11. Meyer D, Birchmeier C. Multiple essential functions of neuregulin in development. Nature. 1995;378:386–390[CrossRef][Medline]
  12. Lee KF, Simon H, Chen H, et al. Requirement for neuregulin receptor erbB2 in neural and cardiac development. Nature. 1995;378:394–399[CrossRef][Medline]
  13. Orioli D, Simon H, Lai C, et al. Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor. Nature. 1995;378:390–394[CrossRef][Medline]
  14. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–793[Abstract/Free Full Text]
  15. Sadoshima J, Izumo S. The cellular and molecular response of cardiac myocytes to mechanical stress. Annu Rev Physiol. 1997;59:551–571[CrossRef][Web of Science][Medline]
  16. Olson TM, Michels VV, Thibodeau SN, et al. Actin mutations in dilated cardiomyopathy, a heritable form of heart failure. Science. 1998;280:750–752[Abstract/Free Full Text]
  17. Dalakas MC, Park KY, Semino-Mora C, et al. Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. N Engl J Med. 2000;342:770–780[Abstract/Free Full Text]
  18. Seidman JG, Seidman CS. The genetic basis for cardiomyopathy myopathy: from mutation identification to mechanistic paradigms. Cell. 2001;104:557–567[CrossRef][Web of Science][Medline]
  19. Dinovâc-Carugo K, Young P, Gautel M, Saraste M. Structure of the alpha-actinin rod: molecular basis for cross-linking of actin filaments. Cell. 1999;98:537–546[CrossRef][Web of Science][Medline]
  20. Coral-Vazquez R, Cohn RD, Moore SA, et al. Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: a novel mechanism for cardiomyopathy and muscular dystrophy. Cell. 1999;98:465–474[CrossRef][Web of Science][Medline]
  21. Bonne G, Di Barletta MR, Varnous S, et al. Mutations in the gene encoding lamin A/C cause amosomal dominant EmeryDreifuss muscular dystrophy. Nat Genet. 1999;21:285–288[CrossRef][Web of Science][Medline]
  22. Tada M, Toyofuku T. Molecular regulation of phospholamban function and expression. Trends Cardiovasc Med. 1998;8:330–340[CrossRef][Web of Science][Medline]
  23. Minamisawa S, Hoshijima M, Chu G, et al. Chronic phospholamban-sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy. Cell. 1999;99:313–322[CrossRef][Web of Science][Medline]
  24. Miyamoto ME, del Monte E, Schmidt U, et al. Adenoviral gene transfer of SERCA2a improves left ventricular function in aortic-banded rats in transition to heart failure. Proc Natl Acad Sci USA. 4th Edition. 2000. p. 793–798
  25. Marx SO, Reiken S, Hisamatsu Y, et al. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell. 2000;101:365–376[CrossRef][Web of Science][Medline]
  26. Curran ME, Sanguinetti MC, Keating MT. Molecular Basis of Inherited Cardiac Arrythmias. Chien KR, Breslow J, Leiden J, Rosenberg R, Seidman CE. Molecular Basis of Cardiovascular Disease (Companion text to E. Braunwald's Heart Disease). 4th Edition. Cambridge, MA: W.B. Saunders Co; 1999. p. 302–311
  27. Gourdie RG, Kubalak S, Mikawa T, et al. Conducting the embryonic heart: Orchestrating development of specialized cardiac tissues. Trends Cardiovasc Med. 1999;9:18–26[CrossRef][Web of Science][Medline]
  28. Zhu H, Nguyen VTB, Brown A, et al. A novel, tissue restricted zinc finger protein (HF-1b) binds to the cardiac regulatory element (HF-1b/MEF-2) in the rat myosin light chain-2 gene. Mol Cell Biol. 1993;13:4432–4444[Abstract/Free Full Text]
  29. Nguyen-Tran VTB, Nguyen-Tran VTB, Kubalak SW, et al. A novel genetic pathway for cardiac sudden death via defects in the transition between ventricular and conduction system cell lineages. Cell. 2000;102:671–682[CrossRef][Web of Science][Medline]
  30. Schott JJ, Benson DW, Basson CT, et al. Congenital heart disease caused by mutations in the transcription factor NKX2–5. Science. 1998;281:108–111[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Chien, K.R.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Chien, K.R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?