Skip to main content
SpringerLink
Log in

Role of Reactive Oxygen Species in the Regulation of Cardiac Myocyte Phenotype

  • Chapter
Pathophysiology of Cardiovascular Disease

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 10))

  • 303 Accesses

Summary

In cardiac myocytes in vitro, ROS can cause either hypertrophy or apoptosis in a concentration-dependent manner with hypertrophy in response to low levels of ROS and apoptosis in response to higher levels. Likewise, there is evidence that ROS mediate the hypertrophic effects of α-adrenergic receptor stimulation and low-level mechanical strain, and the apoptotic effects of β-adrenergic receptor stimulation or higher amplitude mechanical strain. The MAPK signaling pathway appears to mediate several of these effects of ROS. Erk is involved in the hypertrophic response to low levels of ROS, low amplitude mechanical strain and α-adrenergic receptor stimulation. In contrast, JNK is involved in the apoptotic effect of higher levels of ROS, high amplitude mechanical strain and β-adrenergic receptor stimulation. These observations indicate that ROS play a critical role in the determination of myocyte phenotype in response to a variety of stimuli associated with cellular growth or death.

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. Ide T, Tsutsui H, Kinugawa S, Suematsu N, Hayashidani S, Ichikawa K, Utsumi H, Machida Y, Egashira K, Takeshita A. 2000. Direct evidence for increased hydroxyl radicals originating from superoxide in the failing myocardium. Circ Res 86:152–157.

    Article  PubMed  CAS  Google Scholar 

  2. Ghatak A, Brar MJ, Agarwal A, Goel N, Rastogi AK, Vaish AK, Sircar AR, Chandra M. 1996. Oxy free radical system in heart failure and therapeutic role of oral vitamin E. Int J Cardiol 57:119–127.

    Article  CAS  Google Scholar 

  3. Diaz-Velez CR, Garcia-Castineiras S, Mendoza-Ramos E, Hernandez-Lopez E. 1996. Increased malondialdehyde in peripheral blood of patients with congestive heart failure. Am Heart J 131:146–152.

    Article  PubMed  CAS  Google Scholar 

  4. Mallat Z, Philip I, Lebret M, Chatel D, Maclouf J, Tedgui A. 1998. Elevated levels of 8-iso-prostaglandin F2alpha in pericardial fluid of patients with heart failure: a potential role for in vivo oxidant stress in ventricular dilatation and progression to heart failure. Circulation 97:1536–1539.

    Article  PubMed  CAS  Google Scholar 

  5. Gerdes AM, Liu Z, Zimmer HG. 1994. Changes in nuclear size of cardiac myocytes during the development and progression of hypertrophy in rats. Cardioscience 5:203–208.

    PubMed  CAS  Google Scholar 

  6. MacLellan WR, Schneider MD. 1997. Death by design. Programmed cell death in cardiovascular biology and disease. Circ Res 81:137–144.

    Article  PubMed  CAS  Google Scholar 

  7. Weber KT, Anversa P, Armstrong PW, Brilla CG, Burnett JC, Jr, Cruickshank JM, Devereux KB, Giles TD, Korsgaard N, Leier CV, et al. 1992. Remodeling and reparation of the cardiovascular system. J Am Coll Cardiol 20:3–16.

    Article  PubMed  CAS  Google Scholar 

  8. Mann DL, Spinale FG. 1998. Activation of matrix metalloproteinases in the failing human heart: breaking the tie that binds. Circulation 98:1699–1702.

    Article  PubMed  CAS  Google Scholar 

  9. Siwik DA, Tzortzis JD, Pimental DR, Chang DL, Pagano PJ, Singh K, Sawyer DB, Colucci WS. 1999. Inhibition of copper-zinc superoxide dismutase induces cell growth, hypertrophic phenotype, and apoptosis in neonatal rat cardiac myocytes in vitro. Circ Res 85:147–153.

    Article  PubMed  CAS  Google Scholar 

  10. Pimentel DR, Amin JK, Xiao L, Miller T, Viereck J, Oliver-Krasmski J, Baliga R, Wang J, Siwik DA, Singh K, Pagano P, Colucci WS, Sawyer DB. 2001. Reactive oxygen species mediate amplitude-dependent hypertrophic and apoptotic responses to mechanical stretch in cardiac myocytes. Circ Res 89:453–460.

    Article  PubMed  CAS  Google Scholar 

  11. Nakamura K, Fushimi K, Kouchi H, Mihara K, Miyazaki M, Ohe T, Namba M. 1998. Inhibitory effects of antioxidants on neonatal rat cardiac myocyte hypertrophy induced by tumor necrosis factor-alpha and angiotensin II. Circulation 98:794–799.

    Article  PubMed  CAS  Google Scholar 

  12. Amin JK, Xiao L, Pimental DR, Pagano PJ, Singh K, Sawyer DB, Colucci WS. 2001. Reactive oxygen species mediate alpha-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes. J Mol Cell Cardiol 33:131–139.

    Article  PubMed  CAS  Google Scholar 

  13. Cheng TH, Shih NL, Chen SY, Wang DL, Chen JJ. 1999. Reactive oxygen species modulate endothelin-I-induced c-fos gene expression in cardiomyocytes. Cardiovasc Res 41:654–662.

    Article  PubMed  CAS  Google Scholar 

  14. Kometiani P, Li J, Gnudi L, Kahn BB, Askari A, Xie Z. 1998. Multiple signal transduction pathways link Na+/K+-ATPase to growth-related genes in cardiac myocytes. The roles of Ras and mitogen-activated protein kinases. J Biol Chem 273:15249–15256.

    Article  PubMed  CAS  Google Scholar 

  15. Tanaka K, Honda M, Takabatake T. 2001. Redox regulation of MAPK pathways and cardiac hypertrophy in adult rat cardiac myocyte. J Am Coll Cardiol 37:676–685.

    Article  PubMed  CAS  Google Scholar 

  16. Xiao L, Pimentel DR, Wang J, Singh K, Colucci WS, Sawyer DB. 2002. Role of reactive oxygen species and NAD(P)H oxidase in alpha(1)-adrenoceptor signaling in adult rat cardiac myocytes. Am J Physiol Cell Physiol 282:C926–C934.

    Article  PubMed  CAS  Google Scholar 

  17. Griendling KK, Sorescu D, Ushio-Fukai M. 2000. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 86:494–501.

    Article  PubMed  CAS  Google Scholar 

  18. Bendall JK, Cave AC, Heymes C, Gall N, Shah AM. 2002. Pivotal role of a gp91(phox)-containing NADPH oxidase in angiotensin II-induced cardiac hypertrophy in mice. Circulation 105:293–296.

    Article  PubMed  CAS  Google Scholar 

  19. Wang HD, Xu S, Johns DG, Du Y, Quinn MT, Cayatte AJ, Cohen KA. 2001. Role of NADPH oxidase in the vascular hypertrophic and oxidative stress response to angiotensin II in mice. Circ Res 88:947–953.

    Article  PubMed  CAS  Google Scholar 

  20. von Harsdorf R, Li PF, Dietz R. 1999. Signaling pathways in reactive oxygen species-induced cardiomyocyte apoptosis. Circulation 99:2934–2941.

    Article  Google Scholar 

  21. Cheng W, Li B, Kajstura J, Li P, Wolin MS, Sonnenblick EH, Hintze TH, Olivetti G, Anversa P. 1995. Stretch-induced programmed myocyte cell death. J Clin Invest 96:2247–2259.

    Article  PubMed  CAS  Google Scholar 

  22. Communal C, Singh K, Pimentel DR, Colucci WS. 1998. Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the beta-adrenergic pathway. Circulation 98: 1329–1334.

    Article  PubMed  CAS  Google Scholar 

  23. Zaugg M, Xu W, Lucchinetti E, Shafiq SA, Jamali NZ, Siddiqui MA. 2000. Beta-adrenergic receptor subtypes differentially affect apoptosis in adult rat ventricular myocytes. Circulation 102:344–350.

    Article  PubMed  CAS  Google Scholar 

  24. Communal C, Singh K, Sawyer DB, Colucci WS. 1999. Opposing effects of beta(1)- and beta(2) adrenergic receptors on cardiac myocyte apoptosis: role of a pertussis toxin-sensitive G protein. Circulation 100:2210–2212.

    Article  PubMed  CAS  Google Scholar 

  25. Communal C, Xie X, Sawyer DB, Singh K, Colucci WS. 2000. Beta-adrenergic receptor-stimulated apoptosis involves mitochondrial pathways and reactive oxygen species. Circulation 102:II–9 (Abstract).

    Google Scholar 

  26. Rajagopalan S, Politi PM, Sinha BK, Myers CE. 1988. Adriamycin-induced free radical formation in the perfused rat heart: implications for cardiotoxicity. Cancer Res 48:4766–4769.

    PubMed  CAS  Google Scholar 

  27. Sawyer DB, Fukazawa R, Arstall MA, Kelly RA. 1999. Daunorubicin-induced apoptosis in rat cardiac myocytes is inhibited by dexrazoxane. Circ Res %19; 84:257–265.

    Article  CAS  Google Scholar 

  28. Aikawa R, Komuro I, Yamazaki T, Zou Y, Kudoh S, Tanaka M, Shiojima I, Hiroi Y, Yazaki Y. 1997. Oxidative stress activates extracellular signal-regulated kinases through Src and Ras in cultured cardiac myocytes of neonatal rats. J Clin Invest 100:1813–1821.

    Article  PubMed  CAS  Google Scholar 

  29. Sugden PH Clerk A. 1998. “Stress-responsive” mitogen-activated protein kinases (c-Jun N-terminal kinases and p38 mitogen-activated protein kinases) in the myocardium. Circ Res 83:345–352.

    Article  PubMed  CAS  Google Scholar 

  30. Wang Y, Su B, Sah VP, Brown JH, Han J, Chien KR. 1998. Cardiac hypertrophy induced by mitogen-activated protein kinase kinase 7, a specific activator for c-Jun NH2-terminal kinase in ventricular muscle cells. J Biol Chem 273:5423–5426.

    Article  PubMed  CAS  Google Scholar 

  31. Jiang Y, Gram H, Zhao M, New L, Gu J, Feng L, Di Padova F, Ulevitch RJ, Han J. 1997. Characterization of the structure and function of the fourth member of p38 group mitogen-activated protein kinases, p38delta. J Biol Chem 272:30122–30128.

    Article  PubMed  CAS  Google Scholar 

  32. Wei S, Rothstein EC, Fliegel L, Dell’Italia LJ, Lucchesi PA. 2001. Differential MAP kinase activation and Na(+)/H(+) exchanger phosphorylation by H(2)O(2) in rat cardiac myocytes. Am J Physiol Cell Physiol 281:C1542–C1550.

    PubMed  CAS  Google Scholar 

  33. Turner NA, Xia F, Azhar G, Zhang X, Liu L, Wei JY. 1998. Oxidative stress induces DNA fragmentation and caspase activation via the c-Jun NH2-terminal kinase pathway in H9c2 cardiac muscle cells. J Mol Cell Cardiol 30:1789–1801.

    Article  PubMed  CAS  Google Scholar 

  34. Yue TL, Ma XL, Gu JL, Ruffolo RR, Jr, Feuerstein GZ. 1998. Carvedilol inhibits activation of stress-activated protein kinase and reduces reperfusion injury in perfused rabbit heart. Eur J Pharmacol 345:61–65.

    Article  PubMed  CAS  Google Scholar 

  35. Xiao L, Pimental DR, Amin JK, Singh K, Sawyer DB, Colucci WS. 2001. MEK1/2-ERK1/2 mediates alpha1-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes. J Mol Cell Cardiol 33:779–787.

    Article  PubMed  CAS  Google Scholar 

  36. Reed JC. 1997. Cytochrome c: can’t live with it—can’t live without it. Cell 91:559–562.

    Article  PubMed  CAS  Google Scholar 

  37. Sawyer DB, Siwik DA, Xiao L, Pimentel DR, Singh K, Colucci WS. 2002. Role of oxidative stress in myocardial hypertrophy and failure. J Mol Cell Cardiol 34:379–388.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center and the Myocardial Biology Unit, Boston University School of Medicine, Boston, MA, USA

    Melanie Maytin, Douglas B. Sawyer & Wilson S. Colucci M.D.

Authors
  1. Melanie Maytin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Douglas B. Sawyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wilson S. Colucci M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wilson S. Colucci M.D. .

Editor information

Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director) (Distinguished Professor and Director)

  2. Philipps University of Marburg, Marburg, Germany

    Heinz Rupp PhD (Professor of Medicine) (Professor of Medicine)

  3. Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Aubie Angel MD (Professor of Internal Medicine) (Professor of Internal Medicine)

  4. Division of Stroke & Vascular Disease St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Grant N. Pierce PhD, FACC (Professor & Director) (Professor & Director)

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Maytin, M., Sawyer, D.B., Colucci, W.S. (2004). Role of Reactive Oxygen Species in the Regulation of Cardiac Myocyte Phenotype. In: Dhalla, N.S., Rupp, H., Angel, A., Pierce, G.N. (eds) Pathophysiology of Cardiovascular Disease. Progress in Experimental Cardiology, vol 10. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0453-5_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-0453-5_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5084-2

  • Online ISBN: 978-1-4615-0453-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation