Role of neuropeptide Y and peroxisome proliferator-activated receptor γ coactivator-1α in stress cardiomyopathy

  • Sunnassee Ananda (阿兰达)
  • Yunyun Wang (王云云)
  • Shaohua Zhu (朱少华)
  • Rongshuai Wang (王荣帅)
  • Xiaowei Zhou (周小伟)
  • Luo Zhuo (卓 荦)
  • Tingyi Sun (孙婷怡)
  • Liang Ren (任 亮)
  • Qian Liu (刘 茜)
  • Hongmei Dong (董红梅)
  • Yan Liu (刘 艳)
  • Liang Liu (刘 良)
Article

Summary

Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via an animal model, whether the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and the amino peptide neuropeptide Y (NPY) play a role in the pathogenesis of this cardiac entity. Male Sprague-Dawley rats in the experimental group were subjected to immobilization in a plexy glass box for 1 h, which was followed by low voltage electric foot shock for about 1 h at 10 s intervals in a cage fitted with metallic rods. After 25 days the rats were sacrificed and sections of their hearts were processed. Hematoxylin-eosin staining of cardiac tissues revealed the characteristic cardiac lesions of stress cardiomyopathy such as contraction band necrosis, inflammatory cell infiltration and fibrosis. The semi-quantitative RT-PCR analysis for PGC-1α mRNA expression showed significant overexpression of PGC1-α in the stress-subjected rats (P<0.05). Fluorescence immunohistochemistry revealed a higher production of NPY in the stress-subjected rats as compared to the control rats (P=0.0027). Thus, we are led to conclude that following periods of intense stress, an increased expression of PGC1-α in the heart and an overflow of NPY may lead to stress cardiomyopathy and even death in susceptible victims. Moreover, these markers can be used to identify stress cardiomyopathy as the cause of sudden death in specific cases.

Key words

stress cardiomyopathy peroxisome proliferator-activated receptor γ coactivator-1alpha neuropeptide Y sudden death forensic pathology 

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References

  1. 1.
    Cebelin MS, Hirsch CS. Human stress cardiomyopathy. Myocardial lesions in victims of homicidal assaults without internal injuries. Hum Pathol, 1980,11(2):123–132PubMedCrossRefGoogle Scholar
  2. 2.
    Macovei L, Coadă G, Constantinescu V, et al. Takotsubo cardiomyopathy. Rev Med Chir Soc Med Nat Iasi, 2012,116(1):139–144PubMedGoogle Scholar
  3. 3.
    Kawai S, Suzuki H, Yamaguchi H, et al. Ampulla cardiomyopathy (“takotsubo” cardiomyopathy) reversible left ventricular dysfunction with ST segment elevation. Jpn Circ J, 2000,64(2):156–159PubMedCrossRefGoogle Scholar
  4. 4.
    Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-elevation myocardial infarction. Ann intern Med, 2004,141(11):858–865PubMedGoogle Scholar
  5. 5.
    Crea F, Lanza GA. Angina pectoris and normal coronary arteries: cardiac syndrome X. Heart, 2004,90(4):457–463PubMedCrossRefGoogle Scholar
  6. 6.
    Bugiardini R, Badimon L, Collins P, et al. Angina, “Normal” Coronary Angiography, and Vascular Dysfunction: Risk Assessment Strategies. PLoS Med, 2007, 4(2):e12PubMedCrossRefGoogle Scholar
  7. 7.
    Wittstein IS. Stress cardiomyopathy: a syndrome of catecholamine-mediated myocardial stunning? Cell Mol Neurobiol, 2012,32(5):847–857PubMedCrossRefGoogle Scholar
  8. 8.
    Lanza GA, Andreotti F, Sestito A, et al. Platelet aggregability in cardiac syndrome X. Eur Heart J, 2001,22(20):1924–1930PubMedCrossRefGoogle Scholar
  9. 9.
    Raju H, Alberg C, Sagoo GS, et al. Inherited cardiomyopathies. BMJ, 2011,21(343):1106–1110Google Scholar
  10. 10.
    Breuer ME, Willems PH, Russel FG, et al. Modeling mitochondrial dysfunctions in the brain: from mice to men. J Inherit Metab Dis, 2012,35(2):193–210PubMedCrossRefGoogle Scholar
  11. 11.
    García-Giménez JL, Gimeno A, Gonzalez-Cabo P, et al. Differential expression of PGC-1α and metabolic sensors suggest age-dependent induction of mitochondrial biogenesis in Friedreich ataxia fibroblasts. PLoS One, 2011,6(6):e20666PubMedCrossRefGoogle Scholar
  12. 12.
    Macario AJ, Conway de Macario E. Sick chaperones, cellular stress, and disease. N Engl Med, 2005,353(14):1489–1501CrossRefGoogle Scholar
  13. 13.
    Salomon P, Halawa B. Levels of neuropeptide Y and thromboxane B2 in patients with variant angina. Pol Arch Med Wewn, 1998,100(4):313–320PubMedGoogle Scholar
  14. 14.
    Leone TC, Lehman JJ, Finck BN, et al. PGC-1a-deficiency causes multi-system energy metabolic derangements: Muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol, 2005,3(4):e101PubMedCrossRefGoogle Scholar
  15. 15.
    Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev, 2004,18(4):357–368PubMedCrossRefGoogle Scholar
  16. 16.
    Puigserver P, Wu Z, Park CW, et al. A cold inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell, 1998,92(6):829–839PubMedCrossRefGoogle Scholar
  17. 17.
    Lehman JJ, Barger PM, Kovacs A, et al. Peroxisome proliferator-activated receptor γ coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest, 2000, 106(7):847–856PubMedCrossRefGoogle Scholar
  18. 18.
    Russell LK, Mansfield CM, Lehman JJ, et al. Cardiac-specific induction of the transcriptional coactivator peroxisome proliferators-activated receptor-γ coactivator-1α promotes mitochondrial biogenesis and reversible cardiomyopathy in a developmental stage dependent manner. Circ Res, 2004,94(4):525–533PubMedCrossRefGoogle Scholar
  19. 19.
    St-Pierre, Lin JD, Krauss S, et al. Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1α and PGC-1β) in muscle cells. J Biol Chem, 2003,278 (29):26597–26603PubMedCrossRefGoogle Scholar
  20. 20.
    Herzig S, Long F, Jhala US, et al. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature, 2001,413 (6852):179–183PubMedCrossRefGoogle Scholar
  21. 21.
    Rhee J, Inoue Y, Yoon JC, et al. Regulation of hepatic fasting response by PPARgamma coactivator-1alpha (PGC-1): requirement for hepatocyte nuclear factor 4alpha in gluconeogenesis. Proc Natl Acad Sci USA, 2003,100(7):4012–4017PubMedCrossRefGoogle Scholar
  22. 22.
    Allen JM, Adrian TE, Tatemoto K, et al. Two novel related peptides, neuropeptide Y (NPY) and peptide YY (PYY) inhibit the contraction of the electrically stimulated mouse vas deferens. Neropeptides, 1982,3(2):71–77CrossRefGoogle Scholar
  23. 23.
    Gu J, Polak JM, Allen JM, et al. High concentrations of a novel peptide, neuropeptide Y, in the innervation of mouse and rat heart. J Histochem Cytochem, 1984,32(5):467–472PubMedCrossRefGoogle Scholar
  24. 24.
    Rudehill A, Sollevi A, Franco-Cereceda A, et al. Neuropeptide Y (NPY) and the pig heart: release and coronary vasoconstrictor effects. Peptides, 1986,7(5):821–826PubMedCrossRefGoogle Scholar
  25. 25.
    Gullestad L, Pernow J, Bjurö T, et al. Differential effects of metoprolol and atenolol to neuropeptide Y blockade in coronary artery disease. Scand Cardiovasc J, 2012,46(1):23–31PubMedCrossRefGoogle Scholar
  26. 26.
    Morgan CA 3rd, Wang S, Southwick SM, et al. Plasma neuropeptide-Y concentrations in humans exposed to military survival training. Biol Psychiatry, 2000,47(10):902–909PubMedCrossRefGoogle Scholar
  27. 27.
    Gómez-Ambrosi J, Frühbeck G, Martínez JA. Rapid in vivo PGC-1 mRNA upregulation in brown adipose tissue of Wistar rats by a β-(3)-adrenergic agonist and lack of effect of leptin. Mol Cell Endocrinol, 2001,176(1–2):85–90PubMedCrossRefGoogle Scholar
  28. 28.
    Finck BN, Kelly DP. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1α) regulatory cascade in cardiac physiology and disease. Circulation, 2007,115(19):2540–2548PubMedCrossRefGoogle Scholar
  29. 29.
    Russell LK, Finck BN, Kelly DP. Mouse models of mitochondrial dysfunction and heart failure. J Mol Cell Cardiol, 2005,38(1):81–91PubMedCrossRefGoogle Scholar
  30. 30.
    Ventura-Clapier R, Garnier A, Veksler V. Energy metabolism in heart failure. J Physiol, 2004,555 (pt1):1–13Google Scholar
  31. 31.
    van Bilsen M, van Nieuwenhoven FA, van der Vusse GJ. Metabolic remodelling of the failing heart: beneficial or detrimental? Cardiovasc Res, 2009,81(3):420–428PubMedCrossRefGoogle Scholar
  32. 32.
    Cocco G, Chu D. Stress-induced cardiomyopathy: A review. Eur J Intern Med, 2007,18(5):369–379PubMedCrossRefGoogle Scholar
  33. 33.
    Sebastiani M, Giordano C, Nediani C, et al. Induction of mitochondrial biogenesis is a maladaptive mechanism in mitochondrial cardiomyopathies. J Am Coll Cardiol, 2007,50(14):1362–1369PubMedCrossRefGoogle Scholar
  34. 34.
    Stoney CM, Hughes JW. Catecholamine stress responses in arterialized blood. Psychophysiology, 2001,38(3):590–593PubMedCrossRefGoogle Scholar
  35. 35.
    Zhang GX, Kimura S, Nishiyama A, et al. Cardiac oxidative stress in acute and chronic isoproterenol-infused rats. Cardiovasc Res, 2005,65(1):230–238PubMedCrossRefGoogle Scholar
  36. 36.
    Chalkias A, Xanthos T. Pathophysiology and pathogenesis of post-resuscitation myocardial stunning. Heart Fail Rev, 2012,17(1):117–128PubMedCrossRefGoogle Scholar
  37. 37.
    Arnold G, Kaiser C, Fischer R. Myofibrillar degeneration—a common type of myocardial lesion and its selective identification by a modified luxol fast blue stain. Pathol Res Pract, 1985,180(4):405–415PubMedCrossRefGoogle Scholar
  38. 38.
    Duflou J, Nickols G, Waite P, et al. Artefactual contraction band necrosis of the myocardium in fatal air crashes. Aviat Space Environ Med, 2006,77 (9):944–999Google Scholar
  39. 39.
    Schröder R, Schoser B. Myofibrillar myopathies: a clinical and myopathological guide. Brain Pathol, 2009,19(3):483–492PubMedCrossRefGoogle Scholar
  40. 40.
    Machackova J, Barta J, Dhalla NS. Myofibrillar remodelling in cardiac hypertrophy, heart failure and cardiomyopathies. Can J Cardiol, 2006,22(11):953–968PubMedCrossRefGoogle Scholar
  41. 41.
    Murakami T, Tanaka N. The physiological significance of coronary aneurysms in Kawasaki disease. EuroIntervention, 2011,7(8):944–947PubMedCrossRefGoogle Scholar
  42. 42.
    Wittstein IS, Thiemann DR, Lima JA, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med, 2005,352(6):539–548PubMedCrossRefGoogle Scholar
  43. 43.
    Silva AP, Xapelli S, Grouzmann E, et al. The putative neuroprotective role of neuropeptide Y in the central nervous system. Curr Drug Targets CNS Neurol Disord, 2005,4(4):331–347PubMedCrossRefGoogle Scholar
  44. 44.
    García-Villalón AL, Padilla J, Fernández N, et al. Effect of neuropeptide Y on the sympathetic contraction of the rabbit central ear artery during cooling. Pflugers Arch, 2000,440(4):548–555PubMedGoogle Scholar
  45. 45.
    Warner MR, Senanayake PD, Ferrario CM, et al. Sympathetic stimulation-evoked overflow of norepinephrine and neuropeptide Y from the heart. Circ Res, 1991,69(2):455–465PubMedCrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Sunnassee Ananda (阿兰达)
    • 1
  • Yunyun Wang (王云云)
    • 1
  • Shaohua Zhu (朱少华)
    • 1
  • Rongshuai Wang (王荣帅)
    • 1
  • Xiaowei Zhou (周小伟)
    • 1
  • Luo Zhuo (卓 荦)
    • 1
  • Tingyi Sun (孙婷怡)
    • 1
  • Liang Ren (任 亮)
    • 1
  • Qian Liu (刘 茜)
    • 1
  • Hongmei Dong (董红梅)
    • 1
  • Yan Liu (刘 艳)
    • 1
  • Liang Liu (刘 良)
    • 1
  1. 1.Department of Forensic Medicine, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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