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Thyroid Hormone Attenuates Vascular Calcification Induced by Vitamin D3 Plus Nicotine in Rats

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An Erratum to this article was published on 14 March 2015

Abstract

Thyroid hormones (THs) including thyroxine (T4) and triiodothyronine (T3) play critical roles in bone remodeling. However, the role and mechanism of THs in vascular calcification (VC) have been unclear. To explore the pathophysiological roles of T3 on VC, we investigated the changes in plasma and aortas of THs concentrations and the effect of T3 on rat VC induced by vitamin D3 plus nicotine (VDN). VDN-treated rat showed decreased plasma T3 content, increased vascular calcium deposition, and alkaline phosphatase (ALP) activity. Administration of T3 (0.2 mg/kg body weight IP) for 10 days greatly reduced vascular calcium deposition and ALP activity in calcified rat aortas when compared with controls. Concurrently, the loss of smooth muscle lineage markers α-actin and SM22a was restored, and the increased bone-associated molecules, such as runt-related transcription factor2 (Runx2), Osterix, and osteopontin (OPN) levels in calcified aorta, were reduced by administration of T3. The suppression of klotho in calcified rat aorta was restored by T3. Methimazole (400 mg/L) blocked the beneficial effect of T3 on VC. These results suggested that T3 can inhibit VC development.

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References

  1. Flamant F, Baxter JD, Forrest D, Refetoff S, Samuels H, Scanlan TS, Vennström B, Samarut J (2006) International Union of Pharmacology. LIX. The pharmacology and classification of the nuclear receptor superfamily: thyroid hormone receptors. Pharmacol Rev 58:705–711

    Article  CAS  PubMed  Google Scholar 

  2. Bassett JH, Williams GR (2008) Critical role of the hypothalamic-pituitary-thyroid axis in bone. Bone 43:418–426

    Article  CAS  PubMed  Google Scholar 

  3. Williams GR (2009) Actions of thyroid hormones in bone. Endokrynol Pol. 60:380–388

    CAS  PubMed  Google Scholar 

  4. O’Shea PJ, Harvey CB, Suzuki H, Kaneshige M, Kaneshige K, Cheng SY, Williams GR (2003) A thyrotoxic skeletal phenotype of advanced bone formation in mice with resistance to thyroid hormone. Mol Endocrinol 17:1410–1424

    Article  PubMed  Google Scholar 

  5. Murphy E, Williams GR (2004) The thyroid and the skeleton. Clin Endocrinol (Oxf) 61:285–298

    Article  CAS  Google Scholar 

  6. Gogakos AI, Duncan Bassett JH, Williams GR (2010) Thyroid and bone. Arch Biochem Biophys 503:129–136

    Article  CAS  PubMed  Google Scholar 

  7. Danzi S, Klein I (2012) Thyroid hormone and the cardiovascular system. Med Clin North Am 96:257–268

    Article  CAS  PubMed  Google Scholar 

  8. Biondi B, Palmieri EA, Lombardi G, Fazio S (2002) Effects of thyroid hormone on cardiac function: the relative importance of heart rate, loading conditions, and myocardial contractility in the regulation of cardiac performance in human hyperthyroidism. J Clin Endocrinol Metab 87:968–974

    Article  CAS  PubMed  Google Scholar 

  9. Kahaly GJ, Dillmann WH (2005) Thyroid hormone action in the heart. Endocr Rev 26:704–728

    Article  CAS  PubMed  Google Scholar 

  10. Klein I, Danzi S (2007) Thyroid disease and the heart. Circulation 116:1725–1735

    Article  PubMed  Google Scholar 

  11. Mizuma H, Murakami M, Mori M (2001) Thyroid hormone activation in human vascular smooth muscle cells: expression of type II iodothyronine deiodinase. Circ Res 88:313–318

    Article  CAS  PubMed  Google Scholar 

  12. Tatar E, Kircelli F, Asci G, Carrero JJ, Gungor O, Demirci MS, Ozbek SS, Ceylan N, Ozkahya M, Toz H, Ok E (2011) Associations of triiodothyronine levels with carotid atherosclerosis and arterial stiffness in hemodialysis patients. Clin J Am Soc Nephrol 6:2240–2246

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Shaw LJ, Raggi P, Berman DS, Callister TQ (2006) Coronary artery calcium as a measure of biologic age. Atherosclerosis 188:112–119

    Article  CAS  PubMed  Google Scholar 

  14. Goettsch C, Hutcheson JD (2013) Aikawa EMicroRNA in cardiovascular calcification: focus on targets and extracellular vesicle delivery mechanisms. Circ Res 112(7):1073–1084

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Shao JS, Cai J, Towler DA (2006) Molecular mechanisms of vascular calcification: lessons learned from the aorta. Arterioscler Thromb Vasc Biol 26:1423–1430

    Article  CAS  PubMed  Google Scholar 

  16. Demer LL, Tintut Y (2008) Vascular calcification: pathobiology of a multifaceted disease. Circulation 117:2938–2948

    Article  PubMed  Google Scholar 

  17. Zhu D, Mackenzie NC, Millán JL, Farquharson C, MacRae VE (2011) The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells. PLoS One 6:e19595

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Tyson KL, Reynolds JL, McNair R, Zhang Q, Weissberg PL, Shanahan CM (2003) Osteo/chondrocytic transcription factors and their target genes exhibit distinct patterns of expression in human arterial calcification. Arterioscler Thromb Vasc Biol 23:489–494

    Article  CAS  PubMed  Google Scholar 

  19. Li X, Yang HY, Giachelli CM (2008) BMP-2 promotes phosphate uptake, phenotypic modulation, and calcification of human vascular smooth muscle cells. Atherosclerosis. 199:271–277

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Nakahara T, Sato H, Shimizu T, Tanaka T, Matsui H, Kawai-Kowase K, Sato M, Iso T, Arai M, Kurabayashi M (2010) Fibroblast growth factor-2 induces osteogenic differentiation through a Runx2 activation in vascular smooth muscle cells. Biochem Biophys Res Commun. 394:243–248

    Article  CAS  PubMed  Google Scholar 

  21. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108:17–29

    Article  CAS  PubMed  Google Scholar 

  22. Pan K, Sun Q, Zhang J, Ge S, Li S, Zhao Y, Yang P (2010) Multilineage differentiation of dental follicle cells and the roles of Runx2 over-expression in enhancing osteoblast/cementoblast-related gene expression in dental follicle cells. Cell Prolif 43:219–228

    Article  CAS  PubMed  Google Scholar 

  23. Lim K, Lu TS, Molostvov G, Lee C, Lam FT, Zehnder D, Hsiao LL (2012) Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23. Circulation 125:2243–2255

    Article  CAS  PubMed  Google Scholar 

  24. Niederhoffer N, Bobryshev YV, Lartaud-Idjouadiene I, Giummelly P, Atkinson J (1997) Aortic calcification produced by vitamin D3 plus nicotine. J Vasc Res 34:386–398

    Article  CAS  PubMed  Google Scholar 

  25. Hyder JA, Allison MA, Criqui MH, Wright CM (2007) Association between systemic calcified atherosclerosis and bone density. Calcif Tissue Int 80:301–306

    Article  CAS  PubMed  Google Scholar 

  26. Toussaint ND, Lau KK, Strauss BJ, Polkinghorne KR, Kerr PG (2008) Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease. Nephrol Dial Transplant 23:586–593

    Article  PubMed  Google Scholar 

  27. Raggi P, Bellasi A, Ferramosca E, Block GA, Muntner P (2007) Pulse wave velocity is inversely related to vertebral bone density in hemodialysis patients. Hypertension 49:1278–1284

    Article  CAS  PubMed  Google Scholar 

  28. Persy V, D’Haese P (2009) Vascular calcification and bone disease: the calcification paradox. Trends Mol Med 15(9):405–416

    Article  CAS  PubMed  Google Scholar 

  29. Kim ES, Shin JA, Shin JY, Lim DJ, Moon SD, Son HY, Han JH (2012) Association between low serum free thyroxine concentrations and coronary artery calcification in healthy euthyroid subjects. Thyroid 22(9):870–876

    Article  CAS  PubMed  Google Scholar 

  30. Takamura N, Akilzhanova A, Hayashida N, Kadota K, Yamasaki H, Usa T, Nakazato M, Maeda T, Ozono Y, Aoyagi K (2009) Thyroid function is associated with carotid intima-media thickness in euthyroid subjects. Atherosclerosis 204(2):e77–e81

    Article  CAS  PubMed  Google Scholar 

  31. Sato Y, Nakamura R, Satoh M, Fujishita K, Mori S, Ishida S, Yamaguchi T, Inoue K, Nagao T, Ohno Y (2005) Thyroid hormone targets matrix Gla protein gene associated with vascular smooth muscle calcification. Circ Res 97:550–557

    Article  CAS  PubMed  Google Scholar 

  32. Aoshima Y, Mizobuchi M, Ogata H, Kumata C, Nakazawa A, Kondo F, Ono N, Koiwa F, Kinugasa E, Akizawa Vitamin T (2012) D receptor activators inhibit vascular smooth muscle cell mineralization induced by phosphate and TNF-α. Nephrol Dial Transplant 27:1800–1806

    Article  CAS  PubMed  Google Scholar 

  33. Ciceri P, Volpi E, Brenna I, Arnaboldi L, Neri L, Brancaccio D, Cozzolino M (2012) Combined effects of ascorbic acid and phosphate on rat VSMC osteoblastic differentiation. Nephrol Dial Transplant 27:122–127

    Article  CAS  PubMed  Google Scholar 

  34. Byon CH, Sun Y, Chen J, Yuan K, Mao X, Heath JM, Anderson PG, Tintut Y, Demer LL, Wang D, Chen Y (2011) Runx2-upregulated receptor activator of nuclear factor κB ligand in calcifying smooth muscle cells promotes migration and osteoclastic differentiation of macrophages. Arterioscler Thromb Vasc Biol 31:1387–1396

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Tanaka T, Sato H, Doi H, Yoshida CA, Shimizu T, Matsui H, Yamazaki M, Akiyama H, Kawai-Kowase K, Iso T, Komori T, Arai M, Kurabayashi M (2008) Runx2 represses myocardin-mediated differentiation and facilitates osteogenic conversion of vascular smooth muscle cells. Mol Cell Biol 28:1147–1160

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Nishio Y, Dong Y, Paris M, O’Keefe RJ, Schwarz EM, Drissi H (2006) Runx2-mediated regulation of the zinc finger Osterix/Sp7 gene. Gene 372:62–70

    Article  CAS  PubMed  Google Scholar 

  37. Lee CH, Huang YL, Liao JF, Chiou WF (2011) Ugonin K promotes osteoblastic differentiation and mineralization by activation of p38 MAPK- and ERK-mediated expression of Runx2 and osterix. Eur J Pharmacol 668:383–389

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Sciences Foundation of China (Grant no. 81370972 to BH. Zhang and 30600232 to J. Zhang).

Conflict of Interest

Jing Zhang, Jin-Rui Chang, Xiao-Hui Duan, Yan-Rong Yu, and Bao-Hong Zhang of the paper have no financial and personal relationships with other people or organizations that could inappropriately influence this work.

Human and Animal Rights and Informed Consent

All animal care and experimental protocols complied with the Animal Management Rule of the Ministry of Health, People’s Republic of China (Document No. 55, 2001).

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Authors and Affiliations

  1. School of P.E. and Sports Science, Beijing Normal University, Beijing, 100875, China

    Jing Zhang

  2. Laboratory of Cardiovascular Bioactive Molecules, School of Basic Medical Sciences, Peking University, Beijing, 100191, China

    Jin-Rui Chang, Xiao-Hui Duan & Yan-Rong Yu

  3. Hospital of Tsinghua University, Beijing, 100084, China

    Bao-Hong Zhang

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  1. Jing Zhang
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  2. Jin-Rui Chang
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Correspondence to Jing Zhang or Bao-Hong Zhang.

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Zhang, J., Chang, JR., Duan, XH. et al. Thyroid Hormone Attenuates Vascular Calcification Induced by Vitamin D3 Plus Nicotine in Rats. Calcif Tissue Int 96, 80–87 (2015). https://doi.org/10.1007/s00223-014-9934-8

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