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Cell Biochemistry and Biophysics

, Volume 76, Issue 3, pp 433–439 | Cite as

Transforming Growth Factor Beta (TFG-β) Concentration Isoforms are Diminished in Acute Coronary Syndrome

  • Jorge Ramón Padilla-Gutiérrez
  • Emmanuel Valdés-Alvarado
  • Saraí Citlalic Rodríguez-Reyes
  • Juan Arellano-Martin
  • Héctor Enrique Flores-Salinas
  • José Francisco Muñoz Valle
  • Yeminia Valle
Original Paper
  • 79 Downloads

Abstract

Acute coronary syndrome (ACS) is the leading cause of death in elderly patients worldwide. Due its participation in apoptosis, fibrosis, and angiogenesis, transforming growth factor-β (TGF-β) isoforms had been categorized as risk factors for cardiovascular diseases. However, due their contradictory activities, a cardioprotective role has been suggested. The aim was to measure the plasma levels of TGF-β1, 2, and 3 proteins in patients with ACS. This was a case–control study including 225 subjects. The three activated isoforms were measured in serum using the Bio-Plex Pro TGF-β assay by means of magnetic beads; the fluorescence intensity of reporter signal was read in a Bio-Plex Magpix instrument. We observed a significant reduction of the three activated isoforms of TGF-β in patients with ACS. The three TGF-β isoforms were positively correlated with each other in moderate-to-strong manner. TGFβ-2 was inversely correlated with glucose and low-density lipoprotein (LDL)-cholesterol, whereas TGF-β3 was inversely correlated with the serum cholesterol concentration. The production of TGF-β1, TGF-β2, and TGF-β3 are decreased in the serum of patients with ACS. Further follow-up controlled studies with a larger sample size are needed, in order to test whether TGF-β isoforms could be useful as biomarkers that complement the diagnosis of ACS.

Keywords

Acute coronary syndrome Protein isoforms Serum concentration TGF-β concentration Cardiac diseases 

Notes

Acknowledgements

The authors thank all of the participants in this study

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Kumar, A., & Cannon, C. P. (2009). Acute coronary syndromes: diagnosis and management, part I. Mayo Clinic Proceedings Mayo Clinic, 84, 917–938.CrossRefGoogle Scholar
  2. 2.
    Nagesh, C. M., & Roy, A. (2010). Role of biomarkers in risk stratification of acute coronary syndrome. The Indian Journal of Medical Research, 132, 627–633.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Kamath, D. Y., Xavier, D., Sigamani, A., & Pais, P. (2015). High sensitivity C-reactive protein (hsCRP) & cardiovascular disease: an Indian perspective. The Indian Journal of Medical Research, 142, 261–268.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Letterio, J. J., & Roberts, A. B. (1998). Regulation of immune responses by TGF-beta. Annual Review of Immunology, 16, 137–161.CrossRefPubMedGoogle Scholar
  5. 5.
    Heldin C.-H., Moustakas A. (2016) Signaling receptors for TGF-β family members. Cold Spring Harbor Perspectives in Biology, 8, 22–53.Google Scholar
  6. 6.
    Accornero, F., van Berlo, J. H., Correll, R. N., Elrod, J. W., Sargent, M. A., & York, A., et al. (2015). Genetic analysis of connective tissue growth factor as an effector of transforming growth factor β signaling and cardiac remodeling. Molecular and Cellular Biology, 35, 2154–2164.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Pardali, E., Goumans, M.-J., & ten Dijke, P. (2010). Signaling by members of the TGF-beta family in vascular morphogenesis and disease. Trends in Cell Biology, 20, 556–567.CrossRefPubMedGoogle Scholar
  8. 8.
    Kinlay, S., & Ganz, P. (2000). Relation between endothelial dysfunction and the acute coronary syndrome: implications for therapy. The American Journal of Cardiology, 86, 10J–13J. discussion 13J-14J.CrossRefPubMedGoogle Scholar
  9. 9.
    Jiang, J., Zhang, Y., Peng, K., Wang, Q., Hong, X., & Li, H., et al. (2017). Combined delivery of a TGF-β inhibitor and an adenoviral vector expressing interleukin-12 potentiates cancer immunotherapy. Acta Biomaterialia, 61, 114–123.CrossRefPubMedGoogle Scholar
  10. 10.
    Rosenkranz, S. (2004). TGF-beta1 and angiotensin networking in cardiac remodeling. Cardiovascular Research, 63, 423–432.CrossRefPubMedGoogle Scholar
  11. 11.
    Zhang, Q., Cui, F., Fang, L., Hong, J., Zheng, B., & Zhang, J. Z. (2013). TNF-α impairs differentiation and function of TGF-β-induced Treg cells in autoimmune diseases through Akt and Smad3 signaling pathway. Journal of Molecular Cell Biology, 5, 85–98.CrossRefPubMedGoogle Scholar
  12. 12.
    Ohtsuka, K., Gray, J. D., Stimmler, M. M., Toro, B., & Horwitz, D. A. (1998). Decreased production of TGF-beta by lymphocytes from patients with systemic lupus erythematosus. J Immunol Baltimore Maryland 1950, 160, 2539–2545.Google Scholar
  13. 13.
    Dabek, J., Kułach, A., Monastyrska-Cup, B., & Gasior, Z. (2006). Transforming growth factor beta and cardiovascular diseases: the other facet of the “protective cytokine. Pharmacol Rep PR, 58, 799–805.PubMedGoogle Scholar
  14. 14.
    Frangogiannis, N. G. (2017). The role of transforming growth factor (TGF)-β in the infarcted myocardium. Journal of Thoracic Disease, 9, S52–S63.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Frangogiannis, N. G. (2015). Pathophysiology of myocardial infarction. Compr Physiol, 5, 1841–1875.CrossRefPubMedGoogle Scholar
  16. 16.
    Mukaka, M. M. (2012). Statistics corner: a guide to appropriate use of correlation coefficient in medical research. Malawi Medical Journal, 24, 69–71.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Santibañez, J. F., Quintanilla, M., & Bernabeu, C. (2011). TGF-β/TGF-β receptor system and its role in physiological and pathological conditions. Clinical Science, 121, 233–251.CrossRefPubMedGoogle Scholar
  18. 18.
    Euler, G. (2015). Good and bad sides of TGFβ-signaling in myocardial infarction. Frontiers in Physiology, 6, 66.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Chandra, K. S. (2012). Composite risk scores for acute coronary syndromes. Indian Heart Journal, 64, 270–272.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Liu, Y., Yuan, X., Li, W., Cao, Q., & Shu, Y. (2016). Aspirin-triggered resolvin D1 inhibits TGF-β1-induced EMT through the inhibition of the mTOR pathway by reducing the expression of PKM2 and is closely linked to oxidative stress. International Journal of Molecular Medicine, 38, 1235–1242.CrossRefPubMedGoogle Scholar
  21. 21.
    Ji, Q., Guo, M., Zheng, J., Mao, X., Peng, Y., & Li, S., et al. (2009). Downregulation of T helper cell type 3 in patients with acute coronary syndrome. Archives of Medical Research, 40, 285–293.CrossRefPubMedGoogle Scholar
  22. 22.
    Schaan, B. D., Quadros, A. S., Sarmento-Leite, R., De Lucca, G., Bender, A., & Bertoluci, M. (2007). “Correction:” Serum transforming growth factor beta-1 (TGF-beta-1) levels in diabetic patients are not associated with pre-existent coronary artery disease. Cardiovascular Diabetology, 6, 19.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Tashiro, H., Shimokawa, H., Sadamatu, K., & Yamamoto, K. (2002). Prognostic significance of plasma concentrations of transforming growth factor-beta in patients with coronary artery disease. Coronary Artery Disease, 13, 139–143.CrossRefPubMedGoogle Scholar
  24. 24.
    Herder, C., Peeters, W., Zierer, A., de Kleijn, D. P. V., Moll, F. L., & Karakas, M., et al. (2012). TGF-β1 content in atherosclerotic plaques, TGF-β1 serum concentrations and incident coronary events. European Journal of Clinical Investigation, 42, 329–337.CrossRefPubMedGoogle Scholar
  25. 25.
    Redondo, S., Santos-Gallego, C. G., & Tejerina, T. (2007 Aug). TGF-beta1: a novel target for cardiovascular pharmacology. Cytokine and Growth Factor Reviews, 18, 279–286.CrossRefPubMedGoogle Scholar
  26. 26.
    Madrid-Miller, A., Chávez-Sánchez, L., Careaga-Reyna, G., Borrayo-Sánchez, G., Chávez-Rueda, K., & Montoya-Guerrero, S. A., et al. (2014). Clinical outcome in patients with acute coronary syndrome and outward remodeling is associated with a predominant inflammatory response. BMC Research Notes, 7, 669.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Frantz, S., Hu, K., Adamek, A., Wolf, J., Sallam, A., & Maier, S. K. G., et al. (2008). Transforming growth factor beta inhibition increases mortality and left ventricular dilatation after myocardial infarction. Basic Research in Cardiology, 103, 485–492.CrossRefPubMedGoogle Scholar
  28. 28.
    Okada, H., Takemura, G., Kosai, K., Li, Y., Takahashi, T., & Esaki, M., et al. (2005). Postinfarction gene therapy against transforming growth factor-beta signal modulates infarct tissue dynamics and attenuates left ventricular remodeling and heart failure. Circulation, 111, 2430–2437.CrossRefPubMedGoogle Scholar
  29. 29.
    Chen, C.-L., Liu, I.-H., Fliesler, S. J., Han, X., Huang, S. S., & Huang, J. S. (2007). Cholesterol suppresses cellular TGF-beta responsiveness: implications in atherogenesis. Journal of Cell Science, 120, 3509–3521.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Bugyei-Twum, A., Advani, A., Advani, S. L., Zhang, Y., Thai, K., & Kelly, D. J., et al. (2014). High glucose induces Smad activation via the transcriptional coregulator p300 and contributes to cardiac fibrosis and hypertrophy. Cardiovascular diabetology, 13, 89.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Puskás, L. G., Nagy, Z. B., Giricz, Z., Onody, A., Csonka, C., & Kitajka, K., et al. (2004). Cholesterol diet-induced hyperlipidemia influences gene expression pattern of rat hearts: a DNA microarray study. FEBS Letters, 562, 99–104.CrossRefPubMedGoogle Scholar
  32. 32.
    Han, J., Hajjar, D. P., Tauras, J. M., Feng, J., Gotto, A. M., & Nicholson, A. C. (2000). Transforming growth factor-beta1 (TGF-beta1) and TGF-beta2 decrease expression of CD36, the type B scavenger receptor, through mitogen-activated protein kinase phosphorylation of peroxisome proliferator-activated receptor-gamma. The Journal of Biological Chemistry, 275, 1241–1246.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jorge Ramón Padilla-Gutiérrez
    • 1
  • Emmanuel Valdés-Alvarado
    • 1
  • Saraí Citlalic Rodríguez-Reyes
    • 1
    • 2
  • Juan Arellano-Martin
    • 3
  • Héctor Enrique Flores-Salinas
    • 3
    • 4
  • José Francisco Muñoz Valle
    • 1
  • Yeminia Valle
    • 5
  1. 1.Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de GuadalajaraGuadalajaraMexico
  2. 2.Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de GuadalajaraGuadalajaraMexico
  3. 3.Especialidad en Cardiología IMSS, Centro Universitario de Ciencias de la SaludGuadalajaraMexico
  4. 4.Unidad Médica de Alta Especialidad, Centro Médico Nacional de Occidente, Departamento de CardiologíaInstituto Mexicano del Seguro SocialGuadalajaraMexico
  5. 5.Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de GuadalajaraGuadalajaraMexico

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