24 research outputs found

    Lack of Chemokine Signaling through CXCR5 Causes Increased Mortality, Ventricular Dilatation and Deranged Matrix during Cardiac Pressure Overload

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    RATIONALE: Inflammatory mechanisms have been suggested to play a role in the development of heart failure (HF), but a role for chemokines is largely unknown. Based on their role in inflammation and matrix remodeling in other tissues, we hypothesized that CXCL13 and CXCR5 could be involved in cardiac remodeling during HF. OBJECTIVE: We sought to analyze the role of the chemokine CXCL13 and its receptor CXCR5 in cardiac pathophysiology leading to HF. METHODS AND RESULTS: Mice harboring a systemic knockout of the CXCR5 (CXCR5(-/-)) displayed increased mortality during a follow-up of 80 days after aortic banding (AB). Following three weeks of AB, CXCR5(-/-) developed significant left ventricular (LV) dilatation compared to wild type (WT) mice. Microarray analysis revealed altered expression of several small leucine-rich proteoglycans (SLRPs) that bind to collagen and modulate fibril assembly. Protein levels of fibromodulin, decorin and lumican (all SLRPs) were significantly reduced in AB CXCR5(-/-) compared to AB WT mice. Electron microscopy revealed loosely packed extracellular matrix with individual collagen fibers and small networks of proteoglycans in AB CXCR5(-/-) mice. Addition of CXCL13 to cultured cardiac fibroblasts enhanced the expression of SLRPs. In patients with HF, we observed increased myocardial levels of CXCR5 and SLRPs, which was reversed following LV assist device treatment. CONCLUSIONS: Lack of CXCR5 leads to LV dilatation and increased mortality during pressure overload, possibly via lack of an increase in SLRPs. This study demonstrates a critical role of the chemokine CXCL13 and CXCR5 in survival and maintaining of cardiac structure upon pressure overload, by regulating proteoglycans essential for correct collagen assembly

    An Overview of the NASA Spring/Summer 2008 Arctic Campaign - ARCTAS (Arctic Research of the Composition of the Troposphere from Aircraft and Satellites)

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    ARCTAS (Arctic Research of the Composition of the Troposphere from Aircraft and Satellites) is a major NASA led airborne field campaign being performed in the spring and summer of 2008 at high latitudes (http://cloud1.arc.nasa.gov/arctas/). ARCTAS is a part of the International Polar Year program and its activities are closely coordinated with multiple U. S. (NOAA, DOE), Canadian, and European partners. Observational data from an ensemble of aircraft, surface, and satellite sensors are closely integrated with models of atmospheric chemistry and transport in this experiment. Principal NASA airborne platforms include a DC-8 for detailed atmospheric composition studies, a P-3 that focuses on aerosols and radiation, and a B-200 that is dedicated to remote sensing of aerosols. Satellite validation is a central activity in all these platforms and is mainly focused on CALIPSO, Aura, and Aqua satellites. Major ARCTAS themes are: (1) Long-range transport of pollution to the Arctic including arctic haze, tropospheric ozone, and persistent pollutants such as mercury; (2) Boreal forest fires and their implications for atmospheric composition and climate; (3) Aerosol radiative forcing from arctic haze, boreal fires, surface-deposited black carbon, and other perturbations; and (4) Chemical processes with focus on ozone, aerosols, mercury, and halogens. The spring deployment (April) is presently underway and is targeting plumes of anthropogenic and biomass burning pollution and dust from Asia and North America, arctic haze, stratosphere-troposphere exchange, and ozone photochemistry involving HOx and halogen radicals. The summer deployment (July) will target boreal forest fires and summertime photochemistry. The ARCTAS mission is providing a critical link to enhance the value of NASA satellite observations for Earth science. In this talk we will discuss the implementation of this campaign and some preliminary results

    Higher C-reactive protein and soluble tumor necrosis factor receptor levels are associated with poor physical function and disability: A cross-sectional analysis of a cohort of Late Middle-Aged African Americans

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    Background: This cohort of "late middle-aged" African Americans has an excess of disability. We aimed to determine associations of circulating cytokine receptors (sTNFR1, sTNFR2, and sIL-6R) and C-reactive protein (CRP) with disability, physical function, and body composition. Methods: Stratified sampling of two socioeconomically diverse strata of St Louis, Missouri, occurred in 2000–2001. Inclusion criteria were self-reported black or African American race, born 1936–1950 inclusive, and Mini-Mental State Examination score of 16 or greater. In-home evaluations of handgrip strength, lean body mass percentage (LBM%), physical performance, upper and lower body functional limitations (UBFLs and LBFLs), and basic and instrumental activities of daily living (BADLs and IADLs) were collected. Of the 998 participants, 368 had blood sampled at baseline. Serum was stored and assayed in 2006. Results: Absolute risks were LBFLs of 2 or more, 46%; UBFLs of 1 or more, 23.5%; BADLs of 2 or more, 20.6%; and IADLs of 2 or more, 22.5%. Independent of age, sex, and underlying comorbid conditions, higher CRP and sTNFR were associated with poorer physical performance (β = −1.462, p < .001 and β = −0.618, p = .003), UBFLs (odds ratio [OR] 2.26, 95% confidence interval [CI] 1.1–4.64 and OR 1.39, 95% CI 0.96–2.02), LBFLs (OR 2.30, 95% CI 1.19–4.45 and OR 1.91, 95% CI 1.26–2.91), BADLs (OR 2.79, 95% CI 1.03–5.96 and OR 1.66, 95% CI 1.11–2.46), and IADLs (OR 2.13, 95% CI 1.03–4.41 and OR 1.43, 95% CI 0.99–2.08). Higher CRP (β = −3.251, p <.001), sIL-6R (β = −6.152, p = .013), and lower adiponectin (β = 2.947, p = .052) were associated with lower LBM%. Conclusions: Higher CRP and sTNFR are independently associated with disability and physical dysfunction. Higher sIL-6R, CRP, and lower adiponectin associate with lower LBM%.Matthew T. Haren, Theodore K. Malmstrom, Douglas K. Miller, Ping Patrick, H. M. Perry, Margaret M. Herning, William A. Banks and John E. Morle
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