Objective-Vascular endothelial growth factor (VEGF) exerts proangiogenic action and induces activation of a variety of proangiogenic signaling pathways, including the Rho family small G proteins. However, regulators of the Rho family small G proteins in vascular endothelial cells (ECs) are poorly understood. Here we attempted to clarify the expression, subcellular localization, downstream effectors, and proangiogenic role of FGD5, a member of the FGD family of guanine nucleotide exchange factors. Methods and Results-FGD5 was shown to be selectively expressed in cultured human vascular ECs. Immunofluorescence microscopy showed that the signal for FGD5 was observed at peripheral membrane ruffles and perinuclear regions in human umbilical vein ECs. Overexpression of FGD5 increased Cdc42 activity, whereas knockdown of FGD5 by small interfering RNAs inhibited the VEGF-induced activation of Cdc42 and extracellular signal-regulated kinase. VEGF-promoted capillary-like network formation, permeability, directional movement, and proliferation of human umbilical vein ECs and the reorientation of the Golgi complex during directional cell movement were attenuated by knockdown of FGD5. Conclusion-This

Rationale: 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 ␣ V ␤ 3 . However, how the interaction between VEGFR2 and integrin ␣ V ␤ 3 is regulated is not clear. Objective:To investigate whether Necl-5/poliovirus receptor, an immunoglobulin-like molecule that is known to bind integrin ␣ V ␤ 3 , regulates the interaction between VEGFR2 and integrin ␣ V ␤ 3 , and to clarify the role of Necl-5 in the VEGF-induced angiogenesis. Key Words: cell adhesion molecules Ⅲ angiogenesis Ⅲ peripheral vascular disease A ngiogenesis plays an important role in diverse developmental, physiological, and pathological processes. Angiogenesis is triggered by the interaction of proangiogenic growth factors and extracellular matrix with their receptors. Vascular endothelial growth factor (VEGF) is a major proangiogenic agent that regulates multiple key steps of angiogenesis. VEGF exerts its proangiogenic action by binding to VEGF receptor 2 (VEGFR2). The activity of VEGFR2 is regulated by direct interactions with other cell surface proteins, such as coreceptor neuropilins 1 and adhesion molecules, including VE-cadherin 2 and integrins. 3 Integrins, including integrin ␣ V ␤ 3 , are critically involved in angiogenesis and initiate signals that control cell migration, proliferation, and survival. 4 Receptors such as VEGFR2 and plateletderived growth factor (PDGF) receptor (PDGFR) interact with integrins, and these interactions exhibit synergistic effects and cooperatively regulate diverse intracellular signals that control key cell functions. 3,5,6 However, how the interaction between VEGFR2 and integrin ␣ V ␤ 3 through their extracellular regions is regulated is not known. Methods and Results:Original received September 15, 2011; revision received January 12, 2012; accepted January 18, 2012. In December 2011 Nectins and nectin-like molecules (Necls) are immunoglobulinlike cell adhesion molecules that are essential for the formation of cell-cell adhesions, and these molecules regulate a variety of cellular functions, including cell polarization, differentiation, movement, proliferation, and survival. 7,8 Necls comprise a family with 5 members, Necl-1 to -5, and among these, Necl-5 exhibits distinctive expression profiles. Necl-5 was originally identified as human poliovirus receptor (PVR), also termed CD155, 9,10 and as rodent Tage4, which is overexpressed in rodent colon carcinoma. 11,12 Necl-5 is expressed ubiquitously, but its expression level is extremely low in most adult organs in rodents. 13,14 However, it becomes upregulated in the developing or regenerating liver 15,16 and transformed cells. 17,18 In NIH3T3 cells, Necl-5 forms a complex with integrin ␣ V ␤ 3 and PDGFR, and the formation of this complex enhances cell movement and proliferation. 19 However, the function of Necl-5 and its mode of action in vascular endothelial ...

Background: Osteoblast-like differentiation of vascular smooth muscle cells (VSMCs) is a mechanism of vascular calcification. Results: Bone morphogenetic protein endothelial cell precursor-derived regulator (BMPER) was expressed in VSMCs and enhanced osteoblast-like differentiation of VSMCs via NF-B activation. Conclusion: BMPER is a novel regulator of osteoblast-like differentiation of VSMCs. Significance: BMPER may be a potential target for prevention of vascular calcification.

A 29-year-old male who underwent a complete tetralogy of Fallot repair at 2 years of age was referred to our hospital for treatment of sustained ventricular tachycardia (VT). The bipolar voltage map using an electroanatomical mapping system (CARTO, BiosenseWebster) during sinus rhythm revealed a low voltage area identical to the site of the right ventricular outflow tract (RVOT) patch on the anterior wall of the RVOT. During the tachycardia, the activation wavefront was found to revolve in a counterclockwise manner around the patch in the RVOT. Two radiofrequency catheter ablation (RFCA) sessions creating a line between the patch in the RVOT and pulmonary artery achieved only transient success. He underwent a pulmonary valve replacement and reconstruction of the RVOT with a transannular patch to treat the VT refractory to RFCA and severe pressure gradient in the RVOT. In postoperative electrophysiological study, a low voltage area in the RVOT connected to the pulmonary artery with the patch was observed, and produced conduction block in the reentry circuit of the VT. The patient has been free from any VT recurrence during 6 months of follow up. (J Arrhythmia 2008; 24: 156-161)

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