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Expression of transient receptor potential vanilloid genes and proteins in diabetic rat heart

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Abstract

Cardiac complications are leading causes of death in diabetic patients. Imbalance of Ca2+ homeostasis is a hallmark of cardiac dysfunction in diabetes, while TRPV channels are non-selective for cations and are permeable to Ca2+. Our aim was to evaluate the expression levels of TRPV1, TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6 genes and proteins in cardiac tissue at 3 days and 4, 8, and 12 weeks after induction of diabetes. Sprague-Dawley rats were assigned to control and DM groups. DM was induced by intraperitoneal injection of streptozotocin (60 mg/kg). The expression levels of TRPV genes were analyzed by the quantitative reverse transcription polymerase chain reaction, and TRPV proteins were determined by western blotting. Compared to controls, the expression levels of TRPV2, TRPV3, and TRPV6 in diabetic myocardium did not change, while TRPV1 decreased at 4, 8, and 12 weeks, TRPV4 was upregulated at 3 days and 4, 8, and 12 weeks, TRPV5 mRNA increased at 8 and 12 weeks, and TRPV5 protein increased at 4, 8, and 12 weeks. Our findings showed that TRPV1, TRPV4, and TRPV5 are associated with the diabetic heart.

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Abbreviations

DM:

Diabetes mellitus

qRT-PCR:

Quantitative reverse transcription polymerase chain reaction       

RT:

Reverse transcription

PCR:

Polymerase chain reaction

SD:

Standard deviation

STZ:

Streptozotocin

BCA:

Bicinchoninic acid

TRP:

Transient receptor potential

TRPV:

Transient receptor potential vanilloid

ATP:

5'-Adenylate triphosphate

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

References

  1. Mancini GBJ, Cheng AY, Connelly K et al (2017) Diabetes for cardiologists: practical issues in diagnosis and management. Can J Cardiol 33:366–377. https://doi.org/10.1016/j.cjca.2016.07.512

    Article  PubMed  Google Scholar 

  2. Zhang L, Ward M-L, Phillips ARJ et al (2013) Protection of the heart by treatment with a divalent-copper-selective chelator reveals a novel mechanism underlying cardiomyopathy in diabetic rats. Cardiovasc Diabetol 12:123. https://doi.org/10.1186/1475-2840-12-123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Suarez J, Cividini F, Scott BT et al (2018) Restoring mitochondrial calcium uniporter expression in diabetic mouse heart improves mitochondrial calcium handling and cardiac function. J Biol Chem 293:8182–8195. https://doi.org/10.1074/jbc.RA118.002066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Jacobson DA, Philipson LH (2007) TRP channels of the pancreatic beta cell. Handb Exp Pharmacol 179:409–424. https://doi.org/10.1007/978-3-540-34891-7_24

    Article  CAS  Google Scholar 

  5. Falcon D, Galeano-Otero I, Calderon-Sanchez E et al (2019) TRP channels: current perspectives in the adverse cardiac remodeling. Front Physiol 10:159. https://doi.org/10.3389/fphys.2019.00159

    Article  PubMed  PubMed Central  Google Scholar 

  6. Li H (2017) TRP channel classification. Adv Exp Med Biol 976:1–8. https://doi.org/10.1007/978-94-024-1088-4_1

    Article  CAS  PubMed  Google Scholar 

  7. Hof T, Chaigne S, Recalde A et al (2019) Transient receptor potential channels in cardiac health and disease. Nat Rev Cardiol 16:344–360. https://doi.org/10.1038/s41569-018-0145-2

    Article  PubMed  Google Scholar 

  8. Morine KJ, Paruchuri V, Qiao X et al (2016) Endoglin selectively modulates transient receptor potential channel expression in left and right heart failure. Cardiovasc Pathol 25:478–482. https://doi.org/10.1016/j.carpath.2016.08.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Adapala RK, Thoppil RJ, Luther DJ et al (2013) TRPV4 channels mediate cardiac fibroblast differentiation by integrating mechanical and soluble signals. J Mol Cell Cardiol 54:45–52. https://doi.org/10.1016/j.yjmcc.2012.10.016

    Article  CAS  PubMed  Google Scholar 

  10. Heymann HM, Wu Y, Lu Y et al (2017) Transient receptor potential vanilloid 1 inhibitors block laparotomy- and opioid-induced infarct size reduction in rats. Br J Pharmacol 174:4826–4835. https://doi.org/10.1111/bph.14064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Liu Y, Qi H, E M et al (2018) Transient receptor potential vanilloid-3 (TRPV3) activation plays a central role in cardiac fibrosis induced by pressure overload in rats via TGF-beta1 pathway. Naunyn Schmiedeberg’s Arch Pharmacol 391:131–143. https://doi.org/10.1007/s00210-017-1443-7

    Article  CAS  Google Scholar 

  12. Sun T, Guo Z, Liu C-J et al (2016) Preservation of CGRP in myocardium attenuates development of cardiac dysfunction in diabetic rats. Int J Cardiol 220:226–234. https://doi.org/10.1016/j.ijcard.2016.06.092

    Article  PubMed  Google Scholar 

  13. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods (San Diego, CA) 25:402–408. https://doi.org/10.1006/meth.2001.1262

    Article  CAS  Google Scholar 

  14. Morgan JP, Erny RE, Allen PD et al (1990) Abnormal intracellular calcium handling, a major cause of systolic and diastolic dysfunction in ventricular myocardium from patients with heart failure. Circulation 81:III21–III32

    CAS  PubMed  Google Scholar 

  15. Lebeche D, Davidoff AJ, Hajjar RJ (2008) Interplay between impaired calcium regulation and insulin signaling abnormalities in diabetic cardiomyopathy. Nat Clin Pract Cardiovasc Med 5:715–724. https://doi.org/10.1038/ncpcardio1347

    Article  CAS  PubMed  Google Scholar 

  16. Santoni G, Farfariello V, Amantini C (2011) TRPV channels in tumor growth and progression. Adv Exp Med Biol 704:947–967. https://doi.org/10.1007/978-94-007-0265-3_49

    Article  CAS  PubMed  Google Scholar 

  17. Jia Y, Lee L-Y (2007) Role of TRPV receptors in respiratory diseases. Biochim Biophys Acta 1772:915–927. https://doi.org/10.1016/j.bbadis.2007.01.013

    Article  CAS  PubMed  Google Scholar 

  18. Skrzypski M, Billert M, Mergler S et al (2017) Role of TRPV channels in regulating various pancreatic beta-cell functions: lessons from in vitro studies. Biosci Trends 11:9–15. https://doi.org/10.5582/bst.2016.01226

    Article  CAS  PubMed  Google Scholar 

  19. Robbins N, Koch SE, Rubinstein J (2013) Targeting TRPV1 and TRPV2 for potential therapeutic interventions in cardiovascular disease. Transl Res J Lab Clin Med 161:469–476. https://doi.org/10.1016/j.trsl.2013.02.003

    Article  CAS  Google Scholar 

  20. Clapham DE (2003) TRP channels as cellular sensors. Nature 426:517–524. https://doi.org/10.1038/nature02196

    Article  CAS  PubMed  Google Scholar 

  21. Zahner MR, Li D-P, Chen S-R, Pan H-L (2003) Cardiac vanilloid receptor 1-expressing afferent nerves and their role in the cardiogenic sympathetic reflex in rats. J Physiol 551:515–523. https://doi.org/10.1113/jphysiol.2003.048207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Marshall NJ, Liang L, Bodkin J et al (2013) A role for TRPV1 in influencing the onset of cardiovascular disease in obesity. Hypertens (Dallas, TX 1979) 61:246–252. https://doi.org/10.1161/HYPERTENSIONAHA.112.201434

    Article  CAS  Google Scholar 

  23. Lang H, Li Q, Yu H et al (2015) Activation of TRPV1 attenuates high salt-induced cardiac hypertrophy through improvement of mitochondrial function. Br J Pharmacol 172:5548–5558. https://doi.org/10.1111/bph.12987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gao Y, Song J, Chen H et al (2015) TRPV1 activation is involved in the cardioprotection of remote limb ischemic postconditioning in ischemia-reperfusion injury rats. Biochem Biophys Res Commun 463:1034–1039. https://doi.org/10.1016/j.bbrc.2015.06.054

    Article  CAS  PubMed  Google Scholar 

  25. Chen J, Li L, Li Y et al (2015) Activation of TRPV1 channel by dietary capsaicin improves visceral fat remodeling through connexin43-mediated Ca2+ influx. Cardiovasc Diabetol 14:22. https://doi.org/10.1186/s12933-015-0183-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Song J-X, Wang L-H, Yao L et al (2009) Impaired transient receptor potential vanilloid 1 in streptozotocin-induced diabetic hearts. Int J Cardiol 134:290–292

    Article  Google Scholar 

  27. Filosa JA, Yao X, Rath G (2013) TRPV4 and the regulation of vascular tone. J Cardiovasc Pharmacol 61:113–119. https://doi.org/10.1097/FJC.0b013e318279ba42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Randhawa PK, Jaggi AS (2015) TRPV1 and TRPV4 channels: potential therapeutic targets for ischemic conditioning-induced cardioprotection. Eur J Pharmacol 746:180–185. https://doi.org/10.1016/j.ejphar.2014.11.010

    Article  CAS  PubMed  Google Scholar 

  29. Berrout J, Jin M, Mamenko M et al (2012) Function of transient receptor potential cation channel subfamily V member 4 (TRPV4) as a mechanical transducer in flow-sensitive segments of renal collecting duct system. J Biol Chem 287:8782–8791. https://doi.org/10.1074/jbc.M111.308411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mensenkamp AR, Hoenderop JGJ, Bindels RJM (2007) TRPV5, the gateway to Ca2+ homeostasis. Handb Exp Pharmacol 179:207–220. https://doi.org/10.1007/978-3-540-34891-7_12

    Article  CAS  Google Scholar 

  31. de Sousa AR, Penalva LO, Marcotte EM, Vogel C (2009) Global signatures of protein and mRNA expression levels. Mol BioSyst 5:1512–1526. https://doi.org/10.1039/b908315d

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (30872716), the Natural Science Foundation of Hubei Province (2015CFB288), and a Health and Family Planning Project in Hubei Province (WJ2015MB171).

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Contributions

X.L.J. and T.Y. carried out the experiments and drafted the manuscript. C.X. and D.Q.S. was involved in data analysis. M.C.Y., Q.Y.C., J.W., and T.L. contributed to conducting the experiments. Y.Z. and S.Z.Z. reviewed the data, and revised the manuscript.

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Correspondence to Yun Zhao or Shizhong Zhang.

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Jia, X., Yu, T., Xiao, C. et al. Expression of transient receptor potential vanilloid genes and proteins in diabetic rat heart. Mol Biol Rep 48, 1217–1223 (2021). https://doi.org/10.1007/s11033-021-06182-7

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