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Ex Vivo Model for Bioprosthetic Valve Calcification via Stem Cell Differentiation to Bone

Chapter

Abstract

Calcific aortic stenosis is the most common indication for surgical valve replacement in the United States and Europe [1]. Currently, mechanical versus bioprosthetic heart valves are the two options for valve replacement. The choice of valve depends on patient characteristics at the time of surgery [2]. Bioprosthetic heart valves have decreased risk of thrombosis, therefore decreasing the need for anticoagulation. It is estimated that 20–30 % of implanted bioprosthetic heart valves will have some degree of hemodynamic dysfunction at 10 years. For years, the mechanisms of valve degeneration were thought to be due to a passive process in which calcium sticks to the valve directly from the circulation. However, recent studies have demonstrated risk factors for bioprosthetic valve calcification that are similar to vascular atherosclerosis [3, 4]. Furthermore, recent pathologic studies [5] have clearly shown that an inflammatory reaction develops in these calcifying bioprosthesis, which including lipid deposits, inflammatory cell infiltration, and bone matrix proteins expression.

Keywords

Aortic Valve Disease Bioprosthetic Valve Bioprosthetic Heart Valve Calcific Aortic Valve Disease Calcific Aortic Stenosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Roberts WC, Ko JM. Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation. Circulation. 2005;111:920–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Bonow RO, Carabello BA, Kanu C, de Leon Jr AC, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O’Gara PT, O’Rourke RA, Otto CM, Shah PM, Shanewise JS, Smith Jr SC, Jacobs AK, Adams CD, Anderson JL, Antman EM, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Nishimura R, Page RL, Riegel B. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation. 2006;114:e84–231.PubMedCrossRefGoogle Scholar
  3. 3.
    Antonini-Canterin F, Zuppiroli A, Popescu BA, Granata G, Cervesato E, Piazza R, Pavan D, Nicolosi GL. Effect of statins on the progression of bioprosthetic aortic valve degeneration. Am J Cardiol. 2003;92(12):1479–82.Google Scholar
  4. 4.
    Briand M, Lemieux I, Dumesnil JG, Mathieu P, Cartier A, Despres JP, Arsenault M, Couet J, Pibarot P. Metabolic syndrome negatively influences disease progression and prognosis in aortic stenosis. J Am Coll Cardiol. 2006;47:2229–36.PubMedCrossRefGoogle Scholar
  5. 5.
    Shetty R, Pepin A, Charest A, Perron J, Doyle D, Voisine P, Dagenais F, Pibarot P, Mathieu P. Expression of bone-regulatory proteins in human valve allografts. Heart. 2006;92:1303–8.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Rajamannan NM, Subramaniam M, Rickard D, Stock SR, Donovan J, Springett M, Orszulak T, Fullerton DA, Tajik AJ, Bonow RO, Spelsberg T. Human aortic valve calcification is associated with an osteoblast phenotype. Circulation. 2003;107:2181–4 [see comment].PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Caira FC, Stock SR, Gleason TG, McGee EC, Huang J, Bonow RO, Spelsberg TC, McCarthy PM, Rahimtoola SH, Rajamannan NM. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    O’Brien KD, Reichenbach DD, Marcovina SM, Kuusisto J, Alpers CE, Otto CM. Apolipoproteins b, (a), and e accumulate in the morphologically early lesion of ‘degenerative’ valvular aortic stenosis. Arterioscler Thromb Vasc Biol. 1996;16:523–32.PubMedCrossRefGoogle Scholar
  9. 9.
    Tanaka K, Sata M, Fukuda D, Suematsu Y, Motomura N, Takamoto S, Hirata Y, Nagai R. Age-associated aortic stenosis in apolipoprotein e-deficient mice. J Am Coll Cardiol. 2005;46:134–41.PubMedCrossRefGoogle Scholar
  10. 10.
    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.PubMedCentralPubMedGoogle Scholar
  11. 11.
    Wilhelmi MH, Bara C, Kofidis T, Wilhelmi M, Pichlmaier M, Haverich A. Long-term cardiac allograft valves after heart transplant are functionally and structurally preserved, in contrast to homografts and bioprostheses. J Heart Valve Dis. 2006;15:777–82.PubMedGoogle Scholar
  12. 12.
    Wilhelmi MH, Mertsching H, Wilhelmi M, Leyh R, Haverich A. Role of inflammation in allogeneic and xenogeneic heart valve degeneration: immunohistochemical evaluation of inflammatory endothelial cell activation. J Heart Valve Dis. 2003;12:520–6.PubMedGoogle Scholar
  13. 13.
    Skowasch D, Steinmetz M, Nickenig G, Bauriedel G. Is the degeneration of aortic valve bioprostheses similar to that of native aortic valves? Insights into valvular pathology. Expert Rev Med Devices. 2006;3:453–62.PubMedCrossRefGoogle Scholar
  14. 14.
    Bottio T, Thiene G, Pettenazzo E, Ius P, Bortolotti U, Rizzoli G, Valfre C, Casarotto D, Valente M. Hancock ii bioprosthesis: a glance at the microscope in mid-long-term explants. J Thorac Cardiovasc Surg. 2003;126:99–105.PubMedCrossRefGoogle Scholar
  15. 15.
    Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/cbfa1: A transcriptional activator of osteoblast differentiation. Cell. 1997;89:747–54 [see comment].PubMedCrossRefGoogle Scholar
  16. 16.
    Deng ZL, Sharff KA, Tang N, Song WX, Luo J, Luo X, Chen J, Bennett E, Reid R, Manning D, Xue A, Montag AG, Luu HH, Haydon RC, He TC. Regulation of osteogenic differentiation during skeletal development. Front Biosci. 2008;13:2001–21.PubMedCrossRefGoogle Scholar
  17. 17.
    Tintut Y, Alfonso Z, Saini T, Radcliff K, Watson K, Bostrom K, Demer LL. Multilineage potential of cells from the artery wall. Circulation. 2003;108:2505–10.PubMedCrossRefGoogle Scholar
  18. 18.
    Kirton JP, Crofts NJ, George SJ, Brennan K, Canfield AE. Wnt/beta-catenin signaling stimulates chondrogenic and inhibits adipogenic differentiation of pericytes: potential relevance to vascular disease? Circ Res. 2007;101:581–9.PubMedCrossRefGoogle Scholar
  19. 19.
    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.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  1. 1.Division of Biochemistry and Molecular BiologyMayo ClinicRochesterUSA

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