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JCI early table of contents for Mar. 1, 2013

A coordinated response to cardiac stress

Myocardial hypertrophy, a thickening of the heart muscle, is an adaptation that occurs with increased stress on the heart, such as high blood pressure. As the heart muscle expands, it also requires greater blood flow to maintain access to oxygen and nutrients, necessitating an expansion of the cardiac vasculature. In this issue of the Journal of Clinical Investigation, Daniela Tirziu and researchers at Yale University identified a molecular mechanism by which the growth of new blood vessels (angiogenesis) and heart muscle growth are coordinated. Using a mouse model of myocardial hypertrophy, Tirziu and colleagues determined that nitric oxide triggers the destruction of a protein known as RGS4. Nitric oxide typically drives physiological changes associated with the relaxation of blood vessels, while RGS4 attenuates the activity of a cellular signaling pathway that promotes cardiac growth. These findings reveal how increases in heart muscle and blood vessel growth are coordinated, linking changes in vasculature to changes in heart size.

NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth

Daniela Tirziu
Yale School of Medicine, New Haven, CT, USA
Phone: 203-737-2627; Fax: 203-737-6236; E-mail:

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A nanogel-based treatment for lupus

Systemic lupus erythematosus (SLE) is disease in which the immune system mistakenly attacks healthy tissues, resulting in inflammation and tissue damage. Current treatments are focused on suppression of the immune system, but these therapies can leave patients vulnerable to infection. In this issue of the Journal of Clinical Investigation, Tarek Fahmy and colleagues at Yale University report the development of a nanogel-based delivery system that targets an immunosuppressive drug (mycophenolic acid) directly to tissues associated with immune cells. A nanogel is composed of a polymer containing pores that can be loaded with drug compounds. Fahmy and colleagues tested the mycophenolic acid-loaded nanogel in a mouse model of lupus. Mice treated with the nanogel lived longer than untreated mice or mice treated with mycophenolic acid alone. Additionally, the onset of kidney damage, a common complication of lupus, was delayed in nanogel-treated mice. These studies suggest that nanogel-based therapies may be useful in the treatment of SLE.

Nanogel-based delivery of mycophenolic acid ameliorates systemic lupus erythematosus

Tarek Fahmy
Yale University, New Haven, CT, USA
Phone: 203-512-1699; Fax: 203-432-1043; E-mail:

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STAT3 regulates arginase-I in myeloid-derived suppressor cells from cancer patients

Young Kim
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA
Phone: 410-550-0460; E-mail:

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Tumor VEGF:VEGFR2 autocrine feed-forward loop triggers angiogenesis in lung cancer

Roland Ullrich
Max Planck Institute for Neurological Research, Cologne, DEU
Phone: 49-151-62402043; E-mail:

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Blockade of individual Notch ligands and receptors controls graft-versus-host disease

Ivan Maillard
University of Michigan, Ann Arbor, MI, USA
Phone: 734-763-3599; Fax: 734-615-5493; E-mail:

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Formylpeptide receptor-2 contributes to colonic epithelial homeostasis, inflammation, and tumorigenesis

Ji Ming Wang
LMI, CIP, CCR, FNLCR, Frederick, MD, USA
Phone: 301-846-6979; Fax: 301-846-7042; E-mail:

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IgG4 subclass antibodies impair anti-tumor immunity in melanoma

Sophia N Karagiannis
King's College London, London, GBR
Phone: 44-020-7188-6355; Fax: 44-020-7188-8050; E-mail:

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Bone marrow mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression

Irene Ghobrial
Dana-Farber Cancer Institute, Boston, MA, USA
Phone: 617-632-4198; E-mail:

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Contact: Jillian Hurst
Journal of Clinical Investigation

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