Skip to main content
SpringerLink
Log in

Osteocardiology: Cellular Origins of Cardiac Calcification

  • Chapter
  • First Online:
Osteocardiology

  • 267 Accesses

Abstract

The role of circulating stem cells in the development of heterotopic bone formation has been under intense investigation. This chapter summarizes the field to the present and defines experimental models to help further understand the mechanisms of stem cell attachment and mesenchymal differentiation to bone. Finally, it will explore the embryologic origins of cell types in the final common pathway of bone in the valve and in the vessel.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Liu AC, Joag VR, Gotlieb AI. The emerging role of valve interstitial cell phenotypes in regulating heart valve pathobiology. Am J Pathol. 2007;171:1407–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zvaifler NJ, Marinova-Mutafchieva L, Adams G, et al. Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res. 2000;2:477–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kuznetsov SA, Mankani MH, Gronthos S, Satomura K, Bianco P, Robey PG. Circulating skeletal stem cells. J Cell Biol. 2001;153:1133–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Eghbali-Fatourechi GZ, Lamsam J, Fraser D, Nagel D, Riggs BL, Khosla S. Circulating osteoblast-lineage cells in humans. N Engl J Med. 2005;352:1959–66.

    Article  CAS  PubMed  Google Scholar 

  5. Subramaniam M, Cicek M, Pitel KS, et al. TIEG1 modulates beta-catenin sub-cellular localization and enhances Wnt signaling in bone. Nucleic Acids Res. 2017;45:5170–82.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Rajamannan NM. The role of TIEG1 in calcific aortic valve disease. Journal of Bone and Mineral Metabolism. 2017;29(9):S136.

    Google Scholar 

  7. Suda RK, Billings PC, Egan KP, et al. Circulating osteogenic precursor cells in heterotopic bone formation. Stem Cells. 2009;27:2209–19.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Rajamannan NM. Calcific aortic valve disease: cellular origins of valve calcification. Arterioscler Thromb Vasc Biol. 2011;31:2777–8.

    Article  CAS  PubMed  Google Scholar 

  9. Egan KP, Kim JH, Mohler ER 3rd, Pignolo RJ. Role for circulating osteogenic precursor cells in aortic valvular disease. Arterioscler Thromb Vasc Biol. 2011;31:2965–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tanaka K, Sata M, Fukuda D, et al. Age-associated aortic stenosis in apolipoprotein E-deficient mice. J Am Coll Cardiol. 2005;46:134–41.

    Article  CAS  PubMed  Google Scholar 

  11. Dong Y, Lathrop W, Weaver D, et al. Molecular cloning and characterization of LR3, a novel LDL receptor family protein with mitogenic activity. Biochem Biophys Res Commun. 1998;251:784–90.

    Article  CAS  PubMed  Google Scholar 

  12. Brown SD, Twells RC, Hey PJ, et al. Isolation and characterization of LRP6, a novel member of the low density lipoprotein receptor gene family. Biochem Biophys Res Commun. 1998;248:879–88.

    Article  CAS  PubMed  Google Scholar 

  13. Hey PJ, Twells RC, Phillips MS, et al. Cloning of a novel member of the low-density lipoprotein receptor family. Gene. 1998;216:103–11.

    Article  CAS  PubMed  Google Scholar 

  14. Kim DH, Inagaki Y, Suzuki T, et al. A new low density lipoprotein receptor related protein, LRP5, is expressed in hepatocytes and adrenal cortex, and recognizes apolipoprotein E. J Biochem. 1998;124:1072–6.

    Article  CAS  PubMed  Google Scholar 

  15. Gong Y, Slee RB, Fukai N, et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001;107:513–23.

    Article  CAS  PubMed  Google Scholar 

  16. Little RD, Carulli JP, Del Mastro RG, et al. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet. 2002;70:11–9.

    Article  CAS  PubMed  Google Scholar 

  17. Fujino T, Asaba H, Kang MJ, et al. Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion. Proc Natl Acad Sci U S A. 2003;100:229–34.

    Article  CAS  PubMed  Google Scholar 

  18. Rajamannan NM, Subramaniam M, Caira F, Stock SR, Spelsberg TC. Atorvastatin inhibits hypercholesterolemia-induced calcification in the aortic valves via the Lrp5 receptor pathway. Circulation. 2005;112:I229–34.

    PubMed  PubMed Central  Google Scholar 

  19. Caira FC, Stock SR, Gleason TG, et al. Human degenerative valve disease is associated with up-regulation of low-density lipoprotein receptor-related protein 5 receptor-mediated bone formation. J Am Coll Cardiol. 2006;47:1707–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Borrell-Pages M, Romero JC, Badimon L. Cholesterol modulates LRP5 expression in the vessel wall. Atheroslcrosis. 2014;235:363–70.

    Article  CAS  Google Scholar 

  21. Mani A, Radhakrishnan J, Wang H, et al. LRP6 mutation in a family with early coronary disease and metabolic risk factors. Science (New York NY). 2007;315:1278–82.

    Article  CAS  Google Scholar 

  22. Shao JS, Cheng SL, Pingsterhaus JM, Charlton-Kachigian N, Loewy AP, Towler DA. Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals. J Clin Invest. 2005;115:1210–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rajamannan NM. The role of Lrp5/6 in cardiac valve disease: experimental hypercholesterolemia in the ApoE−/− /Lrp5−/− mice. J Cell Biochem. 2011;112:2987–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Boyden LM, Mao J, Belsky J, et al. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002;346:1513–21.

    Article  CAS  PubMed  Google Scholar 

  25. Babij P, Zhao W, Small C, et al. High bone mass in mice expressing a mutant LRP5 gene. J Bone Miner Res. 2003;18:960–74.

    Article  CAS  PubMed  Google Scholar 

  26. Westendorf JJ, Kahler RA, Schroeder TM. Wnt signaling in osteoblasts and bone diseases. Gene. 2004;341:19–39.

    Article  CAS  PubMed  Google Scholar 

  27. Holmen SL, Giambernardi TA, Zylstra CR, et al. Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6. J Bone Miner Res. 2004;19:2033–40.

    Article  CAS  PubMed  Google Scholar 

  28. Phillips HM, Mahendran P, Singh E, Anderson RH, Chaudhry B, Henderson DJ. Neural crest cells are required for correct positioning of the developing outflow cushions and pattern the arterial valve leaflets. Cardiovasc Res. 2013;99:452–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zaniboni A, Bernardini C, Alessandri M, et al. Cells derived from porcine aorta tunica media show mesenchymal stromal-like cell properties in in vitro culture. Am J Physiol Cell Physiol. 2014;306:C322–33.

    Article  CAS  PubMed  Google Scholar 

  30. Leroux-Berger M, Queguiner I, Maciel TT, Ho A, Relaix F, Kempf H. Pathologic calcification of adult vascular smooth muscle cells differs on their crest or mesodermal embryonic origin. J Bone Miner Res. 2011;26:1543–53.

    Article  CAS  PubMed  Google Scholar 

  31. Rajamannan NM, et al. Atorvastatin attenuates bioprosthetic heart valve calcification in a rabbit model via stem cell mediated mechanism, Journal of American College of Cardiology. 2008;51(10):A277.

    Google Scholar 

  32. D’Ippolito G, Diabira S, Howard GA, Menei P, Roos BA, Schiller PC. Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential. J Cell Sci. 2004;117:2971–81.

    Article  PubMed  Google Scholar 

  33. Rajamannan NM, Subramaniam M, Springett M, et al. Atorvastatin inhibits hypercholesterolemia-induced cellular proliferation and bone matrix production in the rabbit aortic valve. Circulation. 2002;105:2260–5.

    Article  Google Scholar 

  34. Rajamannan NM, Subramaniam M, Stock SR, et al. Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve. Heart. 2005;91:806–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Aikawa E, Nahrendorf M, Sosnovik D, et al. Multimodality molecular imaging identifies proteolytic and osteogenic activities in early aortic valve disease. Circulation. 2007;115:377–86.

    Article  CAS  PubMed  Google Scholar 

  36. Weiss RM, Ohashi M, Miller JD, Young SG, Heistad DD. Calcific aortic valve stenosis in old hypercholesterolemic mice. Circulation. 2006;114:2065–9.

    Article  PubMed  Google Scholar 

  37. Rajamannan NM. Embryonic cell origin defines functional role of Lrp5. Atherosclerosis. 2014;236:196–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Most Sacred Heart of Jesus Cardiology and Valvular Institute, Sheboygan, Wisconsin, USA

    Nalini M. Rajamannan

Authors
  1. Nalini M. Rajamannan
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Cite this chapter

Rajamannan, N.M. (2018). Osteocardiology: Cellular Origins of Cardiac Calcification. In: Osteocardiology. Springer, Cham. https://doi.org/10.1007/978-3-319-64994-8_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-64994-8_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-64993-1

  • Online ISBN: 978-3-319-64994-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation