Localization and Characterization of a Novel Secreted Protein, SCUBE2, in the Development and Progression of Atherosclerosis
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概要
- 論文の詳細を見る
Inhibition of atherosclerosis progression has long been the subject of intensive pathophysiologic investigations. The identification of a novel target molecule to redeem the cellular processes remains a major challenge in cardiology. Signal peptide CUB domain EGF-like repeat protein (SCUBE) family has been detected on human tissues and cultured cells. Two members of the SCUBE family, SCUBE1 and SCUBE3 are reported to play a role in cardiovascular diseases. The other member, SCUBE2 has been reported to mediate Hedgehog (Hh) protein signaling and is expressed in major blood vessels during mouse embryogenesis. However its involvement in cardiovascular diseases is not known yet. The aim of this study was to investigate SCUBE2 expression and localization in diffuse intimal thickening (DIT), an early event of atherosclerosis and in advanced lesion of atherosclerotic plaque.Carotid artery ligation in C57BL/6J mice was performed to induce intimal thickening, mimicking DIT in human. After 2 weeks of ligation, mRNA level of SCUBE2 increased significantly, while in LDLr-/- mice fed with high fat diet, a human atherosclerosis model, mRNA level of SCUBE2 expression markedly increased 8 weeks after start of the high fat diet. Our findings were confirmed by the observation of SCUBE2 expression in human coronary artery with DIT and advanced lesion of atherosclerotic plaque. Previous investigations described that SCUBE2 mediates Hh signaling pathway. We have observed that SCUBE2 expression is associated with Sonic Hedgehog (Shh) and its receptor, Patched (Ptc), both in DIT and advanced plaque lesion. Our results suggested that SCUBE2 is a new target molecule in atherosclerosis and might play an important role in atherosclerotic plaque progression via Hh signal transduction.
- 神戸大学の論文
- 2013-00-00
著者
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Emoto Noriaki
Division Of Cardiovascular And Respiratory Medicine Kobe University Graduate School Of Medicine
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Ali Hirowati
Division Of Cardiovascular Medicine Department Of Internal Medicine Kobe University Graduate School
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Hirata Ken-ichi
Division Of Cardiovascular Medicine Department Of Internal Medicine Kobe University Graduate School
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Hatakeyama Kinta
Department Of Clinical Pathology Miyazaki Prefectural Hospital
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Rikitake Yoshiyuki
Division Of Cardiovascular And Respiratory Medicine Department Of Internal Medicine Kobe University
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Asada Yujiro
Department Of Pathology Faculty Of Medicine Miyazaki University
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Ali Hirowati
Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
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Vignon-Zellweger Nicolas
Clinical Pharmacy, Kobe Pharmaceutical University
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Yagi Keiko
Clinical Pharmacy, Kobe Pharmaceutical University
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Nakayama Kazuhiko
Clinical Pharmacy, Kobe Pharmaceutical University
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