Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Estrogen protects male rats from aortic aneurysms

13.10.2004


Study suggests host environment is the critical factor in aneurysm formation

When it comes to abdominal aortic aneurysms – life-threatening bulges or weak areas in the main artery feeding blood to the lower half of the body – new research shows that it is definitely better to be female. During 2000, about 11,000 people in the United States died from a ruptured abdominal aortic aneurysm. Eighty percent of these aneurysms, which doctors call AAAs for short, occur in men. Scientists know very little about why this often-undetected condition, for which there is no medical treatment, strikes men more often than women. But vascular surgeons at the University of Michigan Medical School have found some intriguing clues.

At this week’s American College of Surgeons meeting in New Orleans, Derek T. Woodrum, M.D., a U-M resident in general surgery, will present new research results showing that smooth muscle cells from aortas of male rats contain 2.5 times more destructive MMP-9 protein and 10 times the level of MMP-9 gene expression compared to the same cells from female rat aortas. Known to be involved in AAA formation, MMP-9 is a cell-digesting enzyme that eats away at the wall of the aorta, leaving it vulnerable to expansion and rupture. However, when Woodrum treated male rats with estradiol, a form of the female hormone estrogen, and then tested their aortas, he found that MMP-9 activity was substantially decreased. At this year’s meeting, Woodrum will receive an American College of Surgeons "Excellence in Research Award" for his study.



Woodrum conducted his research in the laboratory of Gilbert Upchurch, M.D., an associate professor of surgery in the U-M Medical School, who studies factors responsible for gender differences in abdominal aortic aneurysms. "Earlier studies have demonstrated that increased estrogen systemically inhibits the development of AAAs," Upchurch says. "Dr. Woodrum’s study extends earlier research and suggests that there also is something inherent in males that increases MMP-9 and may lead to greater AAA formation."

"Estrogen affects production of MMP-9 by white blood cells called macrophages," Upchurch adds. "MMPs degrade collagen and elastin, two major proteins in the aortic wall. Typically production of MMP’s are part of the body’s natural healing response to injury, but left unchecked, MMPs – in particular MMP-9 – can cause extensive tissue damage and lead to the formation of an aneurysm."

In a recent paper published in Atheriosclerosis, Thrombosis and Vascular Biology, Upchurch described a series of U-M experiments focused on gender differences in AAA formation and estrogen’s protective effect. This study was one of the first to include both female and male experimental animals and to compare results between sexes.

The ATVB paper describes how scientists in the Upchurch laboratory first perfused the aortas of male and female rats with elastase, an enzyme that triggers an uncontrolled inflammatory reaction and creates an aneurysm in the aortic wall. Fourteen days later, 82 percent of the male rats, but only 29 percent of the female rats, showed evidence of AAA formation. Macrophages from male rats were shown to be responsible for the higher levels of the MMP-9 enzyme.

In a second group of experiments, U-M scientists surgically transplanted aortas from male to male rats, from female to male, and from female to female. After the rats were treated with elastase to stimulate aneurysm formation, scientists compared the effects on the transplanted aortas. All male aortas transplanted into male rats developed an aneurysm, while only 17 percent of female aortas transplanted into female rats did so. But when female aortas were transplanted into male rats, the protective effect disappeared. Every male rat that received a female aorta developed an aneurysm. "The fact that all the male and female aortas developed aneurysms when transplanted into male rats, compared to only 17 percent of the female aortas in female rats, suggests that host environment is the critical factor in aneurysm formation," Upchurch says.

In the third part of the study, Upchurch and his research team implanted a slow-release estrogen pellet in half the male rats, while the other half went through the same implantation procedure, but did not receive the pellet. After being exposed to elastase perfusion, the scientists compared the effects on aortas from each group. All the male rats developed aneurysms, but the estradiol-treated rats had significantly smaller aneurysms and less damage to the aortic wall than the control rats.

Even though his results provide strong evidence for an estrogen-mediated protective effect, Upchurch cautions that it does not mean everyone should start taking estrogen to protect against AAAs. "There is no medical therapy for abdominal aortic aneurysms," he says. "But understanding exactly what triggers them and how they develop could lead to an effective therapy someday. It also could help us identify people with a high risk of AAA formation who need regular diagnostic testing."

Scientists in Upchurch’s lab are studying other factors involved in AAAs, including how tamoxifen, a drug used to treat breast cancer, affects the process of AAA formation. The research was supported by the National Institutes of Health, the Jobst Vascular Research Fund, the Lifeline Foundation and the University of Michigan.

Gorav Ailawadi, M.D., a U-M resident in surgery, was first author of the ATVB paper. Additional U-M collaborators included Jonathan L. Eliason, M.D., Karen J. Roelofs, D.V.M., Indranil Sinha, Kevin K. Hannawa, Eric P. Kaldjian, M.D., Guanyi Lu, M.D., Ph.D., Peter K. Henke, M.D., James C. Stanley, M.D., Stephen J. Weiss, M.D., and Robert W. Thompson.

Sally Pobojewski | EurekAlert!
Further information:
http://www.umich.edu

More articles from Life Sciences:

nachricht Complete skin regeneration system of fish unraveled
24.04.2018 | Tokyo Institute of Technology

nachricht Scientists generate an atlas of the human genome using stem cells
24.04.2018 | The Hebrew University of Jerusalem

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: BAM@Hannover Messe: innovative 3D printing method for space flight

At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.

Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...

Im Focus: Molecules Brilliantly Illuminated

Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.

Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...

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...

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

Quantum Technology for Advanced Imaging – QUILT

24.04.2018 | Information Technology

AWI researchers measure a record concentration of microplastic in arctic sea ice

24.04.2018 | Earth Sciences

Complete skin regeneration system of fish unraveled

24.04.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>