Publications (2)12.85 Total impact
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Article: Necl-5/poliovirus receptor interacts with VEGFR2 and regulates VEGF-induced angiogenesis.
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ABSTRACT: Vascular endothelial growth factor (VEGF), a major proangiogenic agent, exerts its proangiogenic action by binding to VEGF receptor 2 (VEGFR2), the activity of which is regulated by direct interactions with other cell surface proteins, including integrin α(V)β(3). However, how the interaction between VEGFR2 and integrin α(V)β(3) is regulated is not clear. To investigate whether Necl-5/poliovirus receptor, an immunoglobulin-like molecule that is known to bind integrin α(V)β(3), regulates the interaction between VEGFR2 and integrin α(V)β(3), and to clarify the role of Necl-5 in the VEGF-induced angiogenesis. Necl-5-knockout mice displayed no obvious defect in vascular development; however, recovery of blood flow after hindlimb ischemia and the VEGF-induced neovascularization in implanted Matrigel plugs were impaired in Necl-5-knockout mice. To clarify the mechanism of the regulation of angiogenesis by Necl-5, we investigated the roles of Necl-5 in the VEGF-induced angiogenic responses in vitro. Knockdown of Necl-5 by siRNAs in human umbilical vein endothelial cells (HUVECs) inhibited the VEGF-induced capillary-like network formation on Matrigel, migration, and proliferation, and conversely, enhanced apoptosis. Coimmunoprecipitation assays showed the interaction of Necl-5 with VEGFR2, and knockdown of Necl-5 prevented the VEGF-induced interaction of integrin α(V)β(3) with VEGFR2. Knockdown of Necl-5 suppressed the VEGFR2-mediated activation of downstream proangiogenic and survival signals, including Rap1, Akt, and endothelial nitric oxide synthase. These results demonstrate the critical role of Necl-5 in angiogenesis and suggest that Necl-5 may regulate the VEGF-induced angiogenesis by controlling the interaction of VEGFR2 with integrin α(v)β(3), and the VEGFR2-mediated Rap1-Akt signaling pathway.Circulation Research 03/2012; 110(5):716-26. · 9.49 Impact Factor -
Article: Successful steroid therapy for heart failure due to myocarditis associated with primary biliary cirrhosis.
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ABSTRACT: This report concerns a 65-year-old woman with primary biliary cirrhosis (PBC) featuring high titers of M2 antimitochondrial antibody who developed intractable heart failure (HF). Although the etiology is unclear, involvement of skeletal muscles has been reported with PBC as a result of mitochondrial damage from the autoimmune process. In this case, histopathological examination and (18)F-fluorodeoxy glucose-positron emission tomography imaging revealed myocarditis concomitant with myositis. The patient showed favourable response to high-dose corticosteroid administration. To the best of our knowledge, this is the first case of HF with myocarditis and polymyositis associated with asymptomatic PBC who was successfully treated with prednisolone.The Canadian journal of cardiology 02/2012; 28(4):515.e3-6. · 3.36 Impact Factor
