The Expression of Groups IIE and V Phospholipase A<sub>2</sub> is Associated with an Increased Expression of Osteogenic Molecules in Human Calcified Aortic Valves
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- Suzuki Koji
- Department of Internal Medicine 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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- Watanabe Kazuhiro
- Department of Internal Medicine II, University of Yamanashi, Faculty of Medicine
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- Fujioka Daisuke
- Department of Internal Medicine II, University of Yamanashi, Faculty of Medicine
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- Nakamura Takamitsu
- 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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- Kawabata Ken-ichi
- Department of Internal Medicine II, University of Yamanashi, Faculty of Medicine
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- Katoh Ryohei
- Department of Pathology, University of Yamanashi, Faculty of Medicine
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- Matsumoto Masahiko
- Department of Surgery II, University of Yamanashi, Faculty of Medicine
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- Kugiyama Kiyotaka
- Department of Internal Medicine II, University of Yamanashi, Faculty of Medicine CREST, Japan Science and Technology Agency
Bibliographic Information
- Other Title
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- 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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Abstract
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.<br>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.<br>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.<br>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.
Journal
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- Journal of Atherosclerosis and Thrombosis
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Journal of Atherosclerosis and Thrombosis 21 (12), 1308-1325, 2014
Japan Atherosclerosis Society