my.bionity.com
With an accout for my.bionity.com you can always see everything at a glance – and you can configure your own website and individual newsletter.
Abstract Heart failure is associated with a low grade and chronic cardiac inflammation that impairs function, however the mechanisms by which this sterile inflammation occurs in structural heart disease remain poorly defined. Cardiac‐specific heterozygous overexpression of the calcineurin transgene (CNTg) in mice results in cardiac hypertrophy, inflammation, apoptosis, and ventricular dilation. We hypothesized that activation of the Nlrp3 inflammasome, an intracellular danger sensing pathway required for processing the pro‐inflammatory cytokine interleukin‐1β (IL‐1β), may contribute to myocardial dysfunction and disease progression. Here we report that Nlrp3 mRNA was increased in CNTg mice compared to WT. Consistent with inflammasome activation, CNTg animals had increased conversion of pro‐caspase‐1 to cleaved and activated forms as well as markedly increased serum IL‐1β. Blockade of IL‐1β signaling via chronic IL‐1 receptor antagonist (IL‐1‐ra) therapy reduced cardiac inflammation and myocyte pathology in CNTg mice, resulting in improved systolic performance. Furthermore, genetic ablation of Nlrp3 in CNTg mice reduced pro‐inflammatory cytokine maturation, cardiac inflammation and improved systolic performance. These findings indicate that activation of the Nlrp3 inflammasome in CNTg mice promotes myocardial inflammation and systolic dysfunction through the production of pro‐inflammatory IL‐1β. Blockade of IL‐1β signaling with the IL‐1‐ra reverses these phenotypes, and offers a possible therapeutic approach in the management of heart failure.
| Authors: | Nathan A. Bracey, Paul L. Beck, Daniel A. Muruve, Simon A. Hirota, Jiqing Guo, Habib Jabagi, James R. Wright, Justin A. MacDonald, James P. Lees‐Miller, Daniel Roach, Lisa M. Semeniuk, Henry J. Duff | |
| Journal: | Experimental Physiology | |
| Year: | 2012 | |
| Pages: | no | |
| DOI: | 10.1113/expphysiol.2012.068338 | |
| Publication date: | 29-07-2012 |
Watchlist
This is where you can add this publication to your personal favourites.
Additional Information
Cancer risks for MLH1 and MSH2 mutation carriers
ABSTRACT We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation‐carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer (EC) and other cancers for carriers were estimated using modified segregation analysis co ... more
Scope Flavonoids have well‐known antioxidant, anti‐inflammatory, and anti‐cancer activities. Isoflavone genistein is considered a potent antioxidant agent against oxidative stress. Although several mechanisms have been proposed, a clear antioxidant mechanism of genistein is still remain ... more
Abstract People can get oral cancers from UV (290‐400 nm) exposures. Besides high outdoor UV exposures, high indoor UV exposures to oral tissues can occur when consumers use UV‐emitting tanning devices to either tan or whiten their teeth. We compared the carcinogenic risks of skin to or ... more
Marijuana use may increase risk of testicular cancer
A new study from the University of Southern California (USC) has found a link between recreational marijuana use and an increased risk of developing subtypes of testicular cancer that tend to carry a somewhat worse prognosis. Published in CANCER the findings suggest that the potential cance ... more
New Study into Bladder Regeneration Heralds Organ Replacement Treatment
Researchers in the United States have developed a medical model for regenerating bladders using stem cells harvested from a patient’s own bone marrow. The research, published in STEM CELLS, is especially relevant for paediatric patients suffering from abnormally developed bladders, but also ... more
Stem Cells journal awards human cord-blood research
The journal Stem Cells has announced Dr. Cinzia Rota as the winner of the annual Stem Cells Young Investigator Award. Co-sponsored by the International Stem Cell Symposium, the $10,000 prize is annually given to a young scientist who is the principal author of a research paper published in ... more
Über CHEMIE.DE
CHEMIE.DE Information Service GmbH runs specialist scientific internet portals. The secret to our success? We are familiar with what we publish.
Advertising at CHEMIE.DE
Our advertising formats support you in getting your message across to a clearly defined target audience.
© 1997-2013 CHEMIE.DE Information Service GmbH, All rights reserved
Netmeeting
