The Expression of Groups IIE and V Phospholipase A2 is Associated with an Increased Expression of Osteogenic Molecules in Human Calcified Aortic Valves
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概要
- 論文の詳細を見る
Aim: Eicosanoids play various pathogenic roles in aortic valve calcification. Eicosanoids are derived from the arachidonic acid generated by phospholipase A2 (PLA2). We therefore sought to determine whether PLA2s are expressed in human aortic valves and, if so, whether the expression of PLA2s is related to the expression of osteogenic molecules in these tissues.Methods: Histological and gene expression analyses of 38 non-rheumatic aortic valves obtained at the time of cardiac valve replacement surgery were conducted. Moreover, gene expression analyses were performed using valve interstitial cells (VICs) obtained from human aortic valves.Results: Among the PLA2s examined, the degree of immunoreactivity for PLA2s-IIE and -V was found to significantly correlate with the grade of calcification in the aortic valves. The degree of immunoreactivity and gene expression levels of PLA2s-IIE and -V significantly correlated with those of bone morphogenetic protein (BMP)-2, osteopontin and alkaline phosphatase (ALP). In addition, immunoreactivity for cyclooxygenase (COX)-1, COX-2 and 5-lipoxygenase, downstream enzymes of PLA2 in the arachidonic acid cascade, was co-localized with that for PLA2s-IIE and -V in cells expressing α-smooth muscle actin and macrophages expressing CD68. Furthermore, in the in vitro experiments using cultured VICs, the mRNA expression levels of BMP-2, osteopontin and ALP were suppressed by the inhibition of the expression of PLA2s-IIE or -V with specific siRNAs.Conclusions: The expression of PLA2s-IIE and -V correlates with the development of calcification as well as the expression of pro-osteogenic molecules in human aortic valves, and inhibiting the expression of PLA2s-IIE and -V suppresses the induction of osteogenic molecules in cultured cells. Therefore, PLA2s-IIE and -V may play a role in the pathogenesis of valve calcification.
- 一般社団法人 日本動脈硬化学会の論文
著者
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Katoh Ryohei
Department Of Human Pathology Faculty Of Medicine University Of Yamanashi
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Nakamura Takamitsu
Department of Internal Medicine 2, University of Yamanashi, Faculty of Medicine
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Matsumoto Masahiko
Department Of Biochemistry School Of Medicine Tokai University
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Fujioka Daisuke
Department Of Applied Chemistry Graduate School Of Engineering Osaka City University
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Kugiyama Kiyotaka
Department Of Internal Medicine Ii Interdisciplinary Graduate School Of Medicine And Engineering Uni
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Watanabe Kazuhiro
Department Of Anesthesiology And Critical Care Medicine University Of Tsukuba
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Kawabata Ken-ichi
Department Of Internal Medicine Ii University Of Yamanashi Faculty Of Medicine
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SUZUKI Koji
Department of Agricultural Chemistry, University of the Ryukyus
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Obata Jun-ei
Department of Internal Medicine II, Faculty of Medicine, University of Yamanashi
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Matsumoto Masahiko
Department of Surgery II, University of Yamanashi, Faculty of Medicine
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Takahashi Soichiro
Department of Internal Medicine II, University of Yamanashi, Faculty of Medicine
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Obata Jun-ei
Department of Internal Medicine II, University of Yamanashi, Faculty of Medicine
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