http://content.jci.org/just-published en-us 2008 The American Society for Clinical Investigation http://www.jci.org/icons/banner/rss_title.gif http://content.jci.org Hyung J. Chun, Ziad A. Ali, Yoko Kojima, Ramendra K. Kundu, Ahmad Y. Sheikh, Rani Agrawal, Lixin Zheng, Nicholas J. Leeper, Nathan E. Pearl, Andrew J. Patterson, Joshua P. Anderson, Philip S. Tsao, Michael J. Lenardo, Euan A. Ashley, Thomas Quertermous http://content.jci.org/articles/view/34871 ApoE-KO mice, exogenous Ang II induced atherosclerosis and abdominal aortic aneurysm formation; we found that coinfusion of apelin abrogated these effects. Similarly, apelin treatment rescued Ang II–mediated increases in neointimal formation and vascular remodeling in a vein graft model. NO has previously been implicated in the vasodepressor function of apelin; we found that apelin treatment increased NO bioavailability in ApoE-KO mice. Furthermore, infusion of an NO synthase inhibitor blocked the apelin-mediated decrease in atherosclerosis and aneurysm formation. In rat primary aortic smooth muscle cells, apelin inhibited Ang II–mediated transcriptional regulation of multiple targets as measured by reporter assays. In addition, we demonstrated by coimmunoprecipitation and fluorescence resonance energy transfer analysis that the Ang II and apelin receptors interacted physically. Taken together, these findings indicate that apelin signaling can block Ang II actions in vascular disease by increasing NO production and inhibiting Ang II cellular signaling. ]]> info:doi/10.1172/JCI34871 American Society for Clinical Investigation Gregory D. Lewis, Ru Wei, Emerson Liu, Elaine Yang, Xu Shi, Maryann Martinovic, Laurie Farrell, Aarti Asnani, Marcoli Cyrille, Arvind Ramanathan, Oded Shaham, Gabriel Berriz, Patricia A. Lowry, Igor F. Palacios, Murat Taşan, Frederick P. Roth, Jiangyong Min, Christian Baumgartner, Hasmik Keshishian, Terri Addona, Vamsi K. Mootha, Anthony Rosenzweig, Steven A. Carr, Michael A. Fifer, Marc S. Sabatine, Robert E. Gerszten http://content.jci.org/articles/view/35111 info:doi/10.1172/JCI35111 American Society for Clinical Investigation Shih-Heng Chen, Hui-Wen Yao, I-Te Chen, Biehuoy Shieh, Ching Li, Shun-Hua Chen http://content.jci.org/articles/view/35114 Egr-1 by a DNA-based enzyme greatly reduced the mortality of HSV-1–infected mice by decreasing viral loads in tissues. This study provides what we believe is the first evidence that Egr-1 increases the mortality of HSV-1 encephalitis by enhancing viral replication. Moreover, blocking this cellular machinery exploited by the virus could prevent host mortality. ]]> info:doi/10.1172/JCI35114 American Society for Clinical Investigation Laure Michel, Laureline Berthelot, Ségolène Pettré, Sandrine Wiertlewski, Fabienne Lefrère, Cécile Braudeau, Sophie Brouard, Jean-Paul Soulillou, David-Axel Laplaud http://content.jci.org/articles/view/35365 +CD25^high T cells has been implicated in the pathogenesis of the disease. Here, we reanalyzed the function of this T cell subset in patients with MS, but we depleted cells expressing IL-7 receptor α-chain (CD127), a marker recently described as present on activated T cells but not Tregs. Similar to other studies, we observed a marked defect in the suppressive function of unseparated CD4⁺CD25^high T cells isolated from MS patients. However, when CD127^high cells were removed from the CD4⁺CD25^high population, patient and control cells inhibited T cell proliferation and cytokine production equally. Likewise, when the CD25 gate used to sort the cells was stringent enough to eliminate CD127^high cells, CD4⁺CD25^high T cells from patients with MS and healthy individuals had similar regulatory function. Additional analysis indicated that the CD127^high cells within the CD4⁺CD25^high T cell population from patients with MS appeared more proliferative and secreted more IFN-γ and IL-2 than the same cells from healthy individuals. Taken together, we conclude that CD4⁺CD25^highCD127^low Tregs from MS patients and healthy individuals exhibit similar suppressive functions. The decreased inhibitory function of unfractioned CD4⁺CD25^high cells previously observed might be due to abnormal activation of CD127^high T cells in patients with MS. ]]> info:doi/10.1172/JCI35365 American Society for Clinical Investigation Stefania Corti, Monica Nizzardo, Martina Nardini, Chiara Donadoni, Sabrina Salani, Dario Ronchi, Francesca Saladino, Andreina Bordoni, Francesco Fortunato, Roberto Del Bo, Dimitra Papadimitriou, Federica Locatelli, Giorgia Menozzi, Sandra Strazzer, Nereo Bresolin, Giacomo P. Comi http://content.jci.org/articles/view/35432 info:doi/10.1172/JCI35432 American Society for Clinical Investigation Shao H. Yang, Douglas A. Andres, H. Peter Spielmann, Stephen G. Young, Loren G. Fong http://content.jci.org/articles/view/35876 Lmna^HG/+). The amelioration of disease, however, is incomplete, leading us to hypothesize that nonfarnesylated progerin also might be capable of eliciting disease. To test this hypothesis, we created knockin mice expressing nonfarnesylated progerin (Lmna^nHG/+). Lmna^nHG/+ mice developed the same disease phenotypes observed in Lmna^HG/+ mice, although the phenotypes were milder, and mouse embryonic fibroblasts (MEFs) derived from these mice contained fewer misshapen nuclei. The steady-state levels of progerin in Lmna^nHG/+ MEFs and tissues were lower, suggesting a possible explanation for the milder phenotypes. These data support the concept that inhibition of protein farnesylation in progeria could be therapeutically useful but also suggest that this approach may be limited, as progerin elicits disease phenotypes whether or not it is farnesylated. ]]> info:doi/10.1172/JCI35876 American Society for Clinical Investigation