Angiopoietin-1 Mediates Adipose Tissue-Derived Stem Cell-Induced Inhibition of Neointimal Formation in Rat Femoral Artery

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概要

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• Background: Adipose tissue-derived stem cells (ASC) produce a variety of cytokines that potentially mediate the proangiogenic and antiapoptotic effects of the ASC. We examined whether ASC produced angiopoietin-1 (Ang1) and whether Ang1 functionally mediated ASC-induced suppression of neointimal formation. Methods and Results: Ang1 production was measured by enzyme-linked immunosorbent assay. Production of endogenous Ang1 by ASC was inhibited with small interfering RNA (siRNA) for Ang1. Overproduction of Ang1 was achieved with an adenovirus that expresses Ang1 (AdAng1). ASC expressing Ang1 siRNA, or AdAng1 were administered around the femoral artery after wire injury, and immunohistochemical analysis was performed to examine their effects on neointimal formation. ASC produced Ang1 in a time-dependent manner, especially when cultured in medium containing growth factors for vascular endothelial cells. When ASC were treated with Ang1 siRNA, the inhibitory effect of ASC on neointimal formation was significantly reduced. Knockdown of Ang1 significantly increased macrophage infiltration in the neointima, and significantly decreased endothelial regeneration. In contrast, forced expression of Ang1 using AdAng1 significantly suppressed neointimal formation and macrophage infiltration, and stimulated reendothelialization. Conclusions: Ang1 was implicated in ASC-induced suppression of neointimal formation. The results also suggested that Ang1 inhibited neointimal formation via stimulation of reendothelialization and suppression of macrophage infiltration in the neointima.

• 社団法人　日本循環器学会の論文

著者

• Takahashi Masao

  Department Of Cardiovascular Medicine Graduate School Of Medicine University Of Tokyo

• Suzuki Etsu

  Institute of Medical Science, St. Marianna University School of Medicine

• NAGANO Tetsuo

  Graduate School of Pharmaceutical Sciences, University of Tokyo

• Hirata Yasunobu

  Department Of Advanced Clinical Science And Therapeutics Cardiovascular Medicine Graduate School Of

• Nagano Tetsuo

  Graduate School Of Pharmaceutical Sciences The University Of Tokyo

• Kimura Kenjiro

  Division Of Cardiology Department Of Internal Medicine St. Marianna University School Of Medicine

• Suzuki Etsu

  Institute Of Medical Science St. Marianna University School Of Medicine

• Sato Tomohiko

  Department Of Cardiovascular Medicine Graduate School Of Medicine University Of Tokyo

• Oba Shigeyoshi

  Department Of Internal Medicine Faculty Of Medicine University Of Tokyo

• Kumano Shintaro

  Department Of Urology Faculty Of Medicine University Of Tokyo

• Nishimatsu Hiroaki

  Department of Internal Medicine, Graduate School of Medicine, University of Tokyo

• Kimura Kenjiro

  Division of Nephrology and Hypertension, St. Marianna University School of Medicine

• Takahashi Masao

  Department of Internal Medicine, Faculty of Medicine, University of Tokyo

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