Dysfunctional Mechanisms of Anti-inflammation in Aortic Stenosis

  • David A. FullertonEmail author
  • Xianzhong Meng


Aortic valve disease is the third most common cardiovascular disease in the United States, exceeded only by hypertension and coronary artery disease. Approximately 2–7 % of the population older than 65 years has aortic stenosis [1], and calcific aortic stenosis is the most common indication for valve replacement. Despite its prevalence, the pathogenesis of calcific aortic stenosis is not well understood. In particular, the cellular mechanisms by which the aortic valve leaflets become calcified are unclear.


Aortic Valve Aortic Stenosis Aortic Valve Disease Aortic Valve Leaflet 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.


  1. 1.
    Mohler ER, Gannon F, Reynolds C, et al. Bone formation and inflammation in cardiac valves. Circulation. 2001;103:1522–8.PubMedCrossRefGoogle Scholar
  2. 2.
    O’Brien KD, Knusisto J, Reichenbach DD, et al. Osteopontin is expressed in human aortic valvular lesions. Circulation. 1995;92:2163–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Srivatsa SS, Harrity PJ, Maercklein PB, et al. Increased cellular expression of matrix proteins that regulate mineralization is associated with calcification of native human and porcine xenograft bioprosthetic heart valves. J Clin Invest. 1997;99:996–1009.PubMedCrossRefGoogle Scholar
  4. 4.
    Shao J-S, Cai J, Towler DA. Molecular mechanisms of vascular calcification. Lessons learned from the aorta. Arterioscler Thromb Vasc Biol. 2006;26:1423–30.PubMedCrossRefGoogle Scholar
  5. 5.
    Kaden JJ, Bickelhaupt S, Grobholz R, et al. Expression of bone sialoprotein and bone morphogenetic protein-2 in calcific aortic stenosis. J Heart Valve Dis. 2004;13:560–6.PubMedGoogle Scholar
  6. 6.
    Osman L, Yacoub MH, Latif N, Amrani M, Chester AH. Role of human valve interstitial cells in valve calcification and their response to atorvastatin. Circulation. 2006;114(Suppl I):I-547–52.CrossRefGoogle Scholar
  7. 7.
    Olsson M, Dalsgaard CJ, Haegerstrand A, Rosenqvist M, Ryden L, Nilsson J. Accumulation of T lymphocytes and expression of ­interleukin-2 receptors in nonrheumatic stenotic aortic valves. J Am Coll Cardiol. 1994;23:1162–70.PubMedCrossRefGoogle Scholar
  8. 8.
    Rajamannan NM, Gersh B, Bonow RO. Calcific aortic stenosis: from bench to the bedside-emerging clinical and cellular concepts. Heart. 2003;89:801–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Galante A. C-reactive protein is increased in patients with degenerative aortic valvular stenosis. J Am Coll Cardiol. 2001;38:1078–82.PubMedCrossRefGoogle Scholar
  10. 10.
    Sanchez PL, Mazzone AM. C-reactive protein in aortic valve disease. Cardiovasc Ultrasound. 2006;4:37–40.PubMedCrossRefGoogle Scholar
  11. 11.
    Shahi CN. Elevated levels of circulating soluble adhesion molecules in patients with nonrheumatic aortic stenosis. Am J Cardiol. 1997;79:980–2.PubMedCrossRefGoogle Scholar
  12. 12.
    Karsenty G, Ducy P, Starbuck M, et al. Cbfa1 as a regulator of osteoblast differentiation and function. Bone. 1999;25:107–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Aubin JE, Liu F, Malaval L, et al. Osteoblast and chondroblast differentiation. Bone. 1995;17:77S–83.PubMedCrossRefGoogle Scholar
  14. 14.
    Rajamannan NM, Subramanian M, Rickard D, et al. Human aortic valve calcification is associated with an osteoblast phenotype. Circulation. 2003;107:2181–4.PubMedCrossRefGoogle Scholar
  15. 15.
    Mohler ER, Chawla MK, Chang AW, et al. Identification and characterization of calcifying valve cells from human and canine aortic valves. J Heart Valve Dis. 1999;8:254–60.PubMedGoogle Scholar
  16. 16.
    Lane JM. Bone morphogenic protein science and studies. J Orthop Trauma. 2005;19:S17–22.PubMedCrossRefGoogle Scholar
  17. 17.
    Meng X, Banerjee A, Cleveland JC, Weyant MJ, Dinarello CA, Babu A, et al. Expression of functional Toll-like receptors 2 and 4 in human aortic valve interstitial cells: potential roles in aortic valve inflammation and stenosis. Am J Physiol Cell Physiol. 2008;294:C29–35.PubMedCrossRefGoogle Scholar
  18. 18.
    Babu A, Meng X, Zou N, Yang X, Wang M, Song Y, et al. LPS stimulation of human aortic valve interstitial cells activates inflammation and osteogenesis. Ann Thorac Surg. 2008;86:71–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Yang X, Fullerton DA, Su X, Al L, Meng X. Pro-osteogenic phenotype of human aortic valve interstitial cells is associated with higher levels of Toll-like receptors 2 and 4 and enhanced expression of bone morphogenic proteins. J Am Coll Cardiol. 2009;53:491–500.PubMedCrossRefGoogle Scholar
  20. 20.
    Yang X, Meng X, Su X, Mauchley DC, Ao L, Cleveland JC, et al. Bone morphogenic protein 2 induces Runx2 and osteopontin expression in human aortic valve interstitial cells: role of Smad1 and extracellular signal related kinase 1/2. J Thorac Cardiovasc Surg. 2009;138:1008–15.PubMedCrossRefGoogle Scholar
  21. 21.
    Lee J, Meng X, Weyant MJ, Reece JB, Cleveland Jr JC, Fullerton DA. Stenotic aortic valves have dysfunctional mechanisms of anti-inflammation: implications for aortic stenosis. J Thorac Cardiovasc Surg. 2011;141:481–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Kaden JJ, Dempfle CE, Grobholz R, et al. Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis. Atherosclerosis. 2003;170:205–11.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  1. 1.Division of Cardiothoracic SurgeryThe University of Colorado School of MedicineAuroraUSA

Personalised recommendations