Osteocardiology by Nalini M. Rajamannan

Author:Nalini M. Rajamannan
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

The Molecular Basis of Bone Formation in the Heart

Calcification is largely responsible for hemodynamic progression of aortic valve stenosis. Recent descriptive studies from patient specimens have demonstrated the cell changes associated with aortic valve calcification, including osteoblast expression, cell proliferation, and atherosclerosis [1–4]. Furthermore, these studies have also shown that specific bone cell phenotypes present in calcifying valve tissue from human specimens [5–9] demonstrate the potential for vascular cells to differentiate into calcifying phenotypes.

Recent observations in ex vivo human tissue suggest that rapid advancement in our understanding of the basic mechanisms involved in the initiation and progression of vascular and valvular calcification is now possible. If an osteoblast phenotype is present, then the factors important in the regulation of bone development and regeneration must be considered in the understanding of calcification of the aortic valve. It is well known that cardiovascular calcification is composed of hydroxyapatite deposited on a bone-like matrix of collagen, osteopontin (OP), and other minor bone matrix proteins [2, 10, 11], and regulation occurs via activation of specific transcription factors including MSX2 [12], Runx2 [5], and Sox9 [5]. Calcified aortic valves removed from surgical valve replacement show bone formation (osseous metaplasia) [2, 3, 5]. Further characterization of this phenotype has proven, in calcified bicuspid aortic valves, that immunohistochemistry staining shows the expression of osteopontin [10]. In addition, osteopontin expression has been demonstrated in the mineralization zones of heavily calcified aortic valves obtained at autopsy and surgery [1–3, 5].

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