ヒト大動脈弁石灰化におけるCD34の抑制効果

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  • Inhibitory effect of CD34 on human aortic valve calcification

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<p>While various osteogenic factors induce the ectopic calcification of human aortic valve, the cellular origin of valve calcification remains unclear. Recently, we have demonstrated that human aortic valve interstitial cells (HAVICs) are positive on both mesenchymal stem cell markers (CD73, 90, 105), and endothelial cell marker (VEGFR2), then CD34-negative cells are responsible for aortic valve calcification. While normal HAVICs are physiologically CD34-positive, the pathophysiological role of CD34 in HAVICs obtained from calcified aortic stenosis patients is yet unknown. To confirm whether the transformation from CD34-positive to -negative occurs in HAVICs, we compared the effect of two cytokines; TNF-α and TGF-β. Interestingly, TNF-α unlike TGF-β induced HAVIC calcification, decreasing the gene expression of CD34 and extracellular matrix proteins, tenascin X and MGP. Overexpression of CD34 significantly inhibited TNF-α-induced HAVIC calcification, maintaining tenascin X and MGP gene expression. Further, we confirmed that, in CD34-negative cells, lower expression of tenascin X was shown in comparison to CD34-positive cells by using a DNA microarray. These results suggest that the role of CD34 is to inhibit the HAVIC calcification by maintaining the expression extracellular matrix proteins such as Tenascin X.</p>

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