Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Estrogen-associated COX-2 pathways explain protection from heart disease in female mice

19.11.2004


Implications for chronic use of COX-2 Inhibitors in pre-menopausal women



Heart disease is less pronounced in women than in men as humans age, but this difference narrows after menopause. Some studies have shown that estrogen slows heart disease in mouse models, but the mechanism is largely unknown. Now scientists from the University of Pennsylvania School of Medicine show for the first time that in female mice protection from hardening of the arteries purported to come from higher levels of estrogen acts predominately through cyclooxygenase (COX)-2.

Garret FitzGerald, MD, Chairman of the Department of Pharmacology, and colleagues found that estrogen binds to a cell receptor that activates COX-2, which in turn ramps up the production of the prostacyclin PGI2. This biochemical provides protective benefits both by inhibiting platelet activation and by reducing oxidative stress in the circulatory system by increasing expression of an antioxidant enzyme. Earlier experiments in mice by the FitzGerald lab and others have shown that platelet activation and oxidative stress can independently hasten hardening of the arteries. The most recent findings appear in the November 18 issue of Science.


This study shows for the first time that prostacyclin can modulate gender differences in atherosclerosis and that estrogen increases prostacyclin in an animal model. In addition, this research also demonstrates that estrogen upregulates COX-2-dependent prostacyclin and that prostacyclin contributes to the atheroprotective effect of estrogen.

Disabling the prostacyclin receptor in female mice whose ovaries have been removed took away the atheroprotective effect of estrogen. By taking away the ovaries, the investigators can pinpoint the direct effects of estrogen. In mice treated this way, estrogen, as expected, slows hardening of the arteries. Taking away the receptor for PGI2 in those animals largely undermines this protection, which was based on measuring the extent of atherosclerosis. Increased platelet activation was demonstrated by increased levels of the chemical thromboxane, and increased oxidative stress was measured by increases of isoprostanes in the urine.

Because of the direct links among estrogen, COX-2 pathways, and atheroprotection in female mice, this study raises concern about the use of COX-2 inhibitors in premenopausal women. These studies also raise the possibility of an interaction between hormone replacement therapy and drugs which inhibit COX-2, including traditional NSAIDs. Of particular concern for selective inhibitors of COX-2 would be for patients with juvenile arthritis, which involves mostly long-term drug use in young, premenopausal women, says FitzGerald, also Director of the Institute for Translational Medicine and Therapeutics.

Although researchers extrapolate results from mice to humans with extreme caution, recent studies linking COX-2 inhibitors with cardiovascular risk have focused attention on the possibility of slowly evolving cardiovascular risk during chronic treatment with selective COX-2 inhibitors. This study provides insight into how this risk might occur and identifies potential biomarkers of this evolving risk. The work was funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Other Penn researchers on this paper were Karine M. Egan, John A. Lawson, Susanne Fries, Daniel J. Rader, and Emer M. Smyth, along with Beverley Koller, University of North Carolina.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Life Sciences:

nachricht Rochester scientists discover gene controlling genetic recombination rates
23.04.2018 | University of Rochester

nachricht One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Tiny microenvironments in the ocean hold clues to global nitrogen cycle

23.04.2018 | Earth Sciences

Joining metals without welding

23.04.2018 | Trade Fair News

Researchers illuminate the path to a new era of microelectronics

23.04.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>