Skip to main content

Advertisement

SpringerLink
Log in

Enhanced death signaling in ozone-exposed ischemic-reperfused hearts

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Although numerous advancements made in the field of human health have resulted in reduced deaths due to cardiovascular diseases (CVD), many patients with cardiac disease show no established risk. Therefore, other unknown factors may be responsible for the pathophysiology of CVD. Out of 350,000 sudden cardiac deaths each year in the United States, 60,000 deaths have been related to air pollution, suggesting a detrimental role of environmental pollutants in the development of CVD. The present study tested our hypothesis that chronic ozone exposure enhances the sensitivity to ischemia–reperfusion (I/R) injury in isolated perfused hearts. Sprague-Dawley rats were continuously exposed for 8 h/day for 28 and 56 days to filtered air or 0.8 ppm ozone. Isolated hearts were subjected to 30 min of global ischemia followed by 60 min of reperfusion. Cardiac function after I/R measured as left ventricular developed pressure (LVDP), +dP/dt, –dP/dt, and left ventricular end diastolic pressure (LVEDP) was significantly decreased and increased respectively in ozone-exposed I/R hearts compared to I/R hearts exposed to filtered air. The enhanced sensitivity to I/R injury upon ozone exposure was associated with increased myocardial TNF-α levels and lipid peroxidation and decreased myocardial activities of superoxidase dismutase (SOD) and IL-10. These data suggest that ozone-induced sensitivity to myocardial I/R injury may be due to promoting levels of oxidative stress as well as inflammatory mediators.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Levy D, Wilson P (1998) Atherosclerotic cardiovascular disease: an epidemiological perspective. In: Topol E (ed) Comprehensive cardiovascular medicine. Lippincott-Raven, Philadelphia, PA, pp 27–43

    Google Scholar 

  2. Hennekens C (1998) Increasing burden of cardiovascular disease: current knowledge and future directions for research on risk factors. Circulation 97:1095–1102

    CAS  PubMed  Google Scholar 

  3. Heller RF, Chinn S, Tunstall Pedoe HD, Rose G (1984) How can we predict coronary heart disease? Findings in the United Kingdom Heart Disease Prevention Project. BMJ 288:1409–1411

    Article  CAS  PubMed  Google Scholar 

  4. Mastin JP (2005) Environmental cardiovascular disease. Cardiovasc Toxicol 5:91–94

    Article  CAS  PubMed  Google Scholar 

  5. Gong H Jr, Wong R, Sarma RJ, Linn WS, Sullivan ED, Shamoo DA, Anderson KR, Prasad SB (1998) Cardiovascular effects of ozone exposure in human volunteers. Am J Respir Crit Care Med 158:538–546

    PubMed  Google Scholar 

  6. Sathish Kumar K, Haque M, Perumal TE, Francis J, Uppu RM (2005) A major ozonation product of cholesterol, 3beta-hydroxy-5-oxo-5,6-secocholestan-6-al, induces apoptosis in H9c2 cardiomyoblasts. FEBS Lett 579(28):6444–6450

    Article  CAS  Google Scholar 

  7. Gold DR, Litonjua A, Schwartz J, Lovett E, Larson A, Nearing B, Allen G, Verrier M, Cherry R, Verrier R (2000) Ambient pollution and heart rate variability. Circulation 101(11):1267–1273

    CAS  PubMed  Google Scholar 

  8. Arito H, Uchiyama I, Arakawa H, Yokoyama E (1990) Ozone induced bradycardia and arrhythmia and their relation to sleep-wakefulness in rats. Toxicol Lett 52:169–178

    Article  CAS  PubMed  Google Scholar 

  9. Ruidavets JB, Cournot M, Cassadou S, Giroux M, Meybeck M, Ferrieres J (2005) Ozone air pollution is associated with acute myocardial infarction. Circulation 111:563–569

    Article  CAS  PubMed  Google Scholar 

  10. Di Filippo C, Marfella R, Capodanno P, Ferraraccio F, Coppola L, Luongo M, Mascolo L, Luongo C, Capuano A, Rossi F, D’Amico M (2008) Acute oxygen-ozone administration to rats protects the heart from ischemia reperfusion infarct. Inflamm Res 57:445–449

    Article  CAS  PubMed  Google Scholar 

  11. Merin O, Attias E, Elstein D, Schwalb H, Bitran D, Zimran A, Silberman S (2007) Ozone administration reduces reperfusion injury in an isolated rat heart model. J Card Surg 22:339–342

    Article  PubMed  Google Scholar 

  12. Yang W, Omaya ST (2008) Air pollutants, oxidative stress and human health. Mutat Res, Nov [Epub ahead of print]

  13. Berglind N, Bellander T, Forastiere F, von Klot S, Aalto P, Elosua R, Kulmala M, Lanki T, Löwel H, Peters A, Picciotto S, Salomaa V, Stafoggia M, Sunyer J, Nyberg F, HEAPSS Study Group (2008) Ambient air pollution and daily mortality among survivors of myocardial infarction. Epidemiology 20(1):110–118

    Article  Google Scholar 

  14. Wong CM, Vichit-Vadakan N, Kan H, Qian Z, Ostro B, The PAPA Project Teams (2008) Public health and air pollution in ASIA. Environ Health Perspect 116:1195–1202

    Article  CAS  PubMed  Google Scholar 

  15. Middleton N (2008) A 10 year time-series analysis and cardiovascular mortality in Cyprus. Environ Health 22:39–45

    Article  CAS  Google Scholar 

  16. Medina RM, Schwartz J (2008) Who is more vulnerable to die from ozone air pollution? Epidemiology 19:672–679

    Article  Google Scholar 

  17. Mitis F, Iavarone I, Martuzzi M (2007) Health impact of ozone in 13 Italian cities. Epidemiol Prev 31:323–332

    PubMed  Google Scholar 

  18. Bocci V (2006) Is it true that ozone is always toxic? The end of a dogma. Toxicol Appl Pharmacol 216:493–504

    Article  CAS  PubMed  Google Scholar 

  19. Brooke RD (2008) Cardiovascular effects of air pollution. Clin Sci 115:175–187

    Article  Google Scholar 

  20. Wiester MJ, Tepper JS, King ME, Menache MG, Costa DL (1998) Comparative study of ozone (O3) uptake in three strains of rats and in the guinea pig. Toxicol Appl Pharmacol 96:140–146

    Article  Google Scholar 

  21. Sethi R, Dhalla NS (1995) Inotropic responses to isoproterenol in congestive heart failure subsequent to myocardial infarction in rats. J Card Fail 1(5):391–399

    Article  CAS  PubMed  Google Scholar 

  22. Singla DK, Kaur K, Sharma AK, Dhingra S, Singal PK (2007) Probucol promotes endogenous antioxidant reserve and confers protection against reperfusion injury. Can J Physiol Pharmacol 85:439–443

    Article  CAS  PubMed  Google Scholar 

  23. Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    Article  CAS  PubMed  Google Scholar 

  24. Urich D, Soberanes S, Burgess Z, Chiarella SE, Ghio AJ, Ridge KM, Kamp DW, Chandel NS, Mutlu GM, Budinger GR (2009) Proapoptotic noxa is required for particulate matter-induced cell death and lung inflammation. Faseb J [Epub ahead of print]

  25. Bagate K, Meiring JJ, Gerlofs-Nijland ME, Cassee FR, Wiegand H, Osornio-Vargas A, Borm PJ (2006) Ambient particulate matter affects cardiac recovery in a Langendorff ischemia model. Inhal Toxicol 18:633–643

    Article  CAS  PubMed  Google Scholar 

  26. Cozzi E, Hazarika S, Stallings HW 3rd, Cascio WE, Devlin RB, Lust RM, Wingard CJ, Van Scott MR (2006) Ultrafine particulate matter exposure augments ischemia–reperfusion injury in mice. Am J Physiol 291:H894–H903

    CAS  Google Scholar 

  27. Vancza EM, Galdanes K, Gunnison A, Hatch G, Gordon T (2009) Age, strain, and gender as factors for increased sensitivity of the mouse lung to inhaled ozone. Toxicol Sci 107(2):535–543

    Article  CAS  PubMed  Google Scholar 

  28. Watkinson WP, Campen MJ, Nolan JP, Costa DL (2001) Cardiovascular and systemic responses to inhaled pollutants in rodents: effects of ozone and particulate matter. Environ Health Perspect 109:539–546

    Article  CAS  PubMed  Google Scholar 

  29. Fakhrzadeh L, Laskin JD, Gardner CR, Laskin DL (2003) SOD overexpressing mice are resistant to ozone induced tissue injury and increases in NO and TNF alpha. Am J Respir Cell Mol Biol 30(3):280–287

    Article  PubMed  CAS  Google Scholar 

  30. Chuang KJ, Chan CC, Su TC, Lee CT, Tang CS (2007) The effect of urban air pollution on inflammation, oxidative stress, coagulation, and autonomic dysfunction in young adults. Am J Respir Crit Care Med 176:370–376

    Article  CAS  PubMed  Google Scholar 

  31. Muzykantov VR (2001) Delivery of antioxidant enzyme proteins to the lung. Antioxid Redox Signal 3:39–62

    Article  CAS  PubMed  Google Scholar 

  32. Comhair SA, Erzurum SC (2002) Antioxidant responses to oxidant mediated lung diseases. Am J Physiol lung 283:246–255

    Google Scholar 

  33. Noor R, Mittal S, Iqbal J (2002) Superoxidase dismutase applications and relevance to human disease. Med Sci Monit 8:210–215

    Google Scholar 

  34. Jonsson LM, Edlund T, Marklund SL, Sandström T (2002) Increased ozone-induced airway neutrophilic inflammation in extracellular-superoxide dismutase null mice. Respir Med 96:209–214

    Article  CAS  PubMed  Google Scholar 

  35. Bhalla DK, Reinhart PG, Bai C, Gupta SK (2002) Amelioration of ozone induced lung injury by anti-tumor necrosis factor-alpha. Toxiol Sci 69(2):400–408

    Article  CAS  Google Scholar 

  36. Kapadia SR, Oral H, Lee J, Nakano M, Taffet GE, Mann DL (1997) Hemo-dynamic regulation of tumor necrosis factor-α and protein expression in adult feline myocardium. Circ Res 81:187–195

    CAS  PubMed  Google Scholar 

  37. Meldrum DR, Cleveland JC, Caun BS, Meng X, Harken AH (1998) Increased myocardial TNF-α in a crystalloid perfused model of cardiac ischemic-reperfusion injury. Ann Thorac Surg 65:439–443

    Article  CAS  PubMed  Google Scholar 

  38. Kubota T, McTiernan CF, Frye CS, Slawson SE, Lemster BH, Koretsky AP, Demetris AJ, Feldman A (1997) Dilated cardiomyopathy in transgenic mice with cardiac specific overexpression of TNF-α. Circ Res 81:627–638

    CAS  PubMed  Google Scholar 

  39. Dhingra S, Sharma AK, Arora RC, Slezak J, Singal PK (2009) IL-10 attenuates TNF-{alpha}-induced NF{kappa}B pathway activation and cardiomyocyte apoptosis. Cardiovasc Res, Feb 18 [Epub ahead of print]

  40. Köken T, Serteser M, Kahraman A, Akbulut G, Dilek ON (2004) Which is more effective in the prevention of renal ischemia-reprofusion-induced oxidative injury in the early period in mice: interleukin (IL)-10 or anti-IL-12? Clin Biochem 37:50–55

    Article  PubMed  CAS  Google Scholar 

  41. Das M, Cui J, Das DK (2006) Generation of survival signal by different interaction of p38MAPKalpha and p38MAPKbeta with caveolin-1 and caveolin-3 in the adapted heart. J Mol Cell Cardiol 42(1):206–213

    Article  PubMed  CAS  Google Scholar 

  42. Ballard-Croft C, Locklar AC, Kristo G, Lasley RD (2006) Regional myocardial ischemia-induced activation of MAPKs is associated with subcellular redistribution of caveolin and cholesterol. Am J Physiol 291:H658–H667

    CAS  Google Scholar 

  43. Fakhrzadeh L, Laskin JD, Laskin DL (2007) Regulation of caveolin-1 expression, nitric oxide production and tissue injury by tumour necrosis factor-alpha following ozone inhalation. Toxicol Appl Pharmacol 227:380–389

    Article  PubMed  CAS  Google Scholar 

  44. Murata T, Lin MI, Huang Y, Yu J, Bauer PM, Giordano FJ, Sessa WC (2007) Re-expression of caveolin-1 in endothelium rescues the vascular, cardiac, and pulmonary defects in global caveolin-1 knockout mice. J Exp Med 204(10):2373–2382

    Article  CAS  PubMed  Google Scholar 

  45. Williams AS, Issa R, Durham A, Leung SY, Kapoun A, Medicherla S, Higgins LS, Adcock IM, Chung KF (2008) Role of p38MAPK in ozone-induced airway hyper-responsiveness and inflammation. Eur J Pharmacol 600:117–122

    Article  CAS  PubMed  Google Scholar 

  46. Bhalla DK, Gupta SK, Reinhart PG (1999) Alteration of epithelial integrity, alkaline phosphatase activity and fibronectin expression in lungs of rats exposed to ozone. J Toxicol Environ Health A57:329–343

    Google Scholar 

  47. Dhalla NS, Sethi R, Dakshinamurthi K (2000) Treatment of cardiovascular and related pathologies, United States Patent 6043259

  48. Hatch GE, Slade R, Harris LP, McDonnell WF, Devlin RB, Koren HS, Costa DL, McKee J (1994) Ozone dose and effect in humans and rats: a comparison using oxygen-18 labeling and bronchoalveolar lavage. Am J Respir Crit Care Med 150:676–683

    CAS  PubMed  Google Scholar 

  49. Miller FJ (1995) Uptake and fate of ozone in the respiratory tract. Toxicol Lett 82–83:277–285

    Article  PubMed  Google Scholar 

  50. Rouslin W, Broge CW, Guerrieri F, Capozza G (1995) ATPase activity, IF1 content, and proton conductivity of ESMP from control and ischemic slow and fast heart-rate hearts. J Bioenerg Biomembr 27(4):459–466

    Article  CAS  PubMed  Google Scholar 

  51. Tardif JC, Carrier M, Kandzari DE et al (2007) Effects of pyridoxal-5-phosphate in patients undergoing high risk coronary artery bypass surgery: results of MED-CABG randomized trial. J Thorac Cardovasc Surg 133(6):1604–1611

    Article  CAS  Google Scholar 

  52. Miller JF, Menzel DB, Coffin DL (1978) Similarity between man and laboratory animals in regional pulmonary deposition of ozone. Environ Res 17:84–101

    Article  CAS  PubMed  Google Scholar 

  53. Wiester MJ, Stevens MA, Menache MG, McKee JL Jr, Gerrity TR (1996) Ozone uptake in healthy adult males during quiet breathing. Fundam Appl Toxicol 29:102–109

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from Texas A&M Health Science Center (TAMHSC), Texas A&M University Kingsville (TAMUK) and US Environmental Protection Agency. We thank Dr. Kuruvilla John and Mr. Don Marek from the Department of Environmental Engineering at TAMUK for their technical support and advice. We are also grateful to TAMUK-Ronald McNair Scholars—Miss Patricia Hinojosa and Mr. Daniel Diaz, TAMHSC-Pharm D student—Ms. BaAimee Nguyen and the King High School-AP Biology Student—Mr. Vishal Sethi for laboratory assistance.

Author information

Authors and Affiliations

  1. Department of Biological & Health Sciences, Texas A&M University Kingsville, Kingsville, TX, USA

    Rama Surya Prakash Perepu & Carlos Garcia

  2. Division of Molecular Cardiology, Central Texas Veterans Administration Health Care System, Texas A&M University System Health Science Center, Temple, TX, USA

    David Dostal

  3. Cardiovascular Research and Development Laboratory, Irma Lerma Rangel College of Pharmacy, Texas A&M University System Health Science Center, 1010 West Avenue B, MSC 131, 78363-8202, Kingsville, TX, USA

    Rajat Sethi

Authors
  1. Rama Surya Prakash Perepu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlos Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David Dostal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rajat Sethi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajat Sethi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Perepu, R.S.P., Garcia, C., Dostal, D. et al. Enhanced death signaling in ozone-exposed ischemic-reperfused hearts. Mol Cell Biochem 336, 55–64 (2010). https://doi.org/10.1007/s11010-009-0265-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-009-0265-4

Keywords

Search

Navigation