Comparative in vitro study examined the osteogenic potential of interstitial cells of aortic valve obtained from the patients with aortic stenosis and from control recipients of orthotopic heart transplantation with intact aortic valve. The osteogenic inductors augmented mineralization of aortic valve interstitial cells (AVIC) in patients with aortic stenosis in comparison with the control level. Native AVIC culture of aortic stenosis patients demonstrated overexpression of osteopontin gene (OPN) and underexpression of osteoprotegerin gene (OPG) in comparison with control levels. In both groups, AVIC differentiation was associated with overexpression of RUNX2 and SPRY1 genes. In AVIC of aortic stenosis patients, expression of BMP2 gene was significantly greater than the control level. The study revealed an enhanced sensitivity of AVIC to osteogenic inductors in aortic stenosis patients, which indicates probable implication of OPN, OPG, and BMP2 genes in pathogenesis of aortic valve calcification.
Similar content being viewed by others
References
Bogdanova MA, Gudkova AY, Zabirnik AS, Ignatieva EV, Dmitrieva RI, Smolina NA, Kostareva AA, Malashicheva AB. Nuclear lamins regulate osteogenic differentiation of mesenchymal stem cells. Cell Tissue Biol. 2014;8(4):292-298.
Alexopoulos A, Bravou V, Peroukides S, Kaklamanis L, Varakis J, Alexopoulos D, Papadaki H. Bone regulatory factors NFATc1 and Osterix in human calcific aortic valves. Int. J. Cardiol. 2010;139(2):142-149.
Boström KI, Rajamannan NM, Towler DA. The regulation of valvular and vascular sclerosis by osteogenic morphogens. Circ Res. 2011;109(5):564-577.
Dweck MR, Boon NA, Newby DE. Calcific aortic stenosis: a disease of the valve and the myocardium. J. Am. Coll. Cardiol. 2012;60(19):1854-1863.
Kahles F, Findeisen HM, Bruemmer D. Osteopontin: a novel regulator at the cross roads of inflammation, obesity and diabetes. Mol. Metab. 2014;3(4):384-393.
Liu AC, Joag VR, Gotlieb AI. The emerging role of valve interstitial cell phenotypes in regulating heart valve pathobiology. Am. J. Pathol. 2007;171(5):1407-1418.
Nishimura R, Hata K, Matsubara T, Wakabayashi M, Yoneda T. Regulation of bone and cartilage development by network between BMP signalling and transcription factors. J. Biochem. 2012;151(3):247-254.
Pohjolainen V, Taskinen P, Soini Y, Rysä J, Ilves M, Juvonen T, Ruskoaho H, Leskinen H, Satta J. Noncollagenous bone matrix proteins as a part of calcificaortic valve disease regulation. Hum. Pathol. 2008;39(11):1695-1701.
Rutkovskiy A, Stensløkken KO, Vaage IJ. Osteoblast differentiation at a glance. Med. Sci. Monit. Basic Res. 2016;22:95-106.
Towler DA. Molecular cellular aspects of calcific aortic valve disease. Circ. Res. 2013;113(2):198-208.
Weiss RM, Lund DD, Chu Y, Brooks RM, Zimmerman KA, El Accaoui R, Davis MK, Hajj GP, Zimmerman MB, Heistad DD. Osteoprotegerin inhibits aortic valve calcification and preserves valve function in hypercholesterolemic mice. PLoS One. 2013;8(6):e65201. doi:https://doi.org/10.1371/journal.pone.0065201
Yang X, Harkins LK, Zubanova O, Harrington A, Kovalenko D, Nadeau RJ, Chen PY, Toher JL, Lindner V, Liaw L, Friesel R. Overexpression of Spry1 in chondrocytes causes attenuated FGFR ubiquitination and sustained ERK activation resulting in chondrodysplasia. Dev Biol. 2008;321(1):64-76.
Yutzey KE, Demer LL, Body SC, Huggins GS, Towler DA, Giachelli CM, Hofmann-Bowman MA, Mortlock DP, Rogers MB, Sadeghi MM, Aikawa E. Calcific aortic valve disease: a consensus summary from the Alliance of Investigators on Calcific Aortic Valve Disease. Arterioscler. Thromb. Vasc. Biol. 2014;34(11):2387-2393.
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 164, No. 9, pp. 356-360, September, 2017
Rights and permissions
About this article
Cite this article
Zhiduleva, E.V., Irtyuga, O.B., Shishkova, A.A. et al. Cellular Mechanisms of Aortic Valve Calcification. Bull Exp Biol Med 164, 371–375 (2018). https://doi.org/10.1007/s10517-018-3992-2
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-018-3992-2