Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New evidence links inflammation to venous disease

19.11.2003


Research could lead to new diagnostic tests; safer treatments for blood clots in deep leg veins



For a medical disorder affecting more than 250,000 Americans each year, researchers don’t know much more today about what causes blood clots in veins than they did over 100 years ago. But deep vein thromboses or DVTs are a serious health problem, especially in the elderly. When blood clots form in deep leg veins, they can permanently damage the venous system or even be fatal, if a blood clot, or pulmonary embolism, travels to the lungs.

Until recently, DVT was thought to be solely a blood or vascular disorder. Now, scientists from the University of Michigan Medical School have discovered intriguing new evidence to support the idea that the development of blood clots in veins – just like blocked arteries in atherosclerosis – is an inflammatory process.


"When a blood clot develops in superficial veins of the leg – a condition called phlebitis – the redness and swelling associated with inflammation are visible," says Thomas W. Wakefield, M.D., a scientist and vascular surgeon in the U-M’s Cardiovascular Center. "When a clot forms deep inside the leg, these signs are hidden, so physicians have rarely associated DVTs with inflammation."

Working with Daniel D. Myers, DVM, MPH, an assistant professor of vascular surgery and animal medicine in the U-M Medical School, Wakefield is trying to figure out exactly what happens inside veins when a blood clot develops. In a study published in the November 2003 issue of The Journal of Vascular Surgery, he and Myers report that inflammatory molecules and immune system cells play a major role in the process.

The U-M scientists used four types of mice in the study. The first was a strain of genetically engineered mice developed by co-author Denisa D. Wagner, Ph.D, a professor of pathology at Harvard Medical School. A genetic mutation in these mice causes them to have abnormally high levels of a pro-inflammatory molecule called P-selectin circulating in their blood plasma. In previous studies, Wakefield has found that large amounts of P-selectin are expressed in the vein wall shortly after a blood clot starts to form.

A second group of mice lacked the gene required to produce P-selectin. A third group was unable to express either P-selectin or a related molecule called E-selectin. The fourth group consisted of normal controls. In all, 659 mice were involved in the research study.

Mice were surgically treated to induce thrombosis in the IVC – the major vein carrying blood from the lower body back to the heart. On the second and sixth day after surgery, U-M scientists measured the size and weight of blood clots in the IVC, examined the vein walls and took blood samples from mice in all four groups.

U-M scientists found that mice with the highest levels of P-selectin in their blood developed the largest venous blood clots and had more inflammatory cells in their vein walls. Blood from mice with high levels of P-selectin also contained microparticles – small fragments of cell membrane from degraded cells. Most of these microparticles came from immune system cells called leukocytes, but some were derived from blood platelets, which are responsible for clot initiation. Additionally, some may have come from endothelial cells lining vein walls.

"Our laboratory is the first to evaluate microparticle formation in a mouse model of DVT," Myers says. "We found that when P-selectin binds to its receptor, it seems to release these pro-coagulant microparticles, which accelerate the clot-forming process. Mice with more leukocyte-derived microparticles developed larger blood clots than mice with microparticles derived primarily from blood platelets."

Wakefield says the ultimate goal of his research is finding new ways to inhibit clot formation in his patients by using an anti-inflammatory approach, instead of relying on anticoagulants to treat DVT after it develops.

"All current blood-thinning medications can cause serious bleeding problems in patients, so there’s a need for new treatment options," he says. "The more we understand about the mechanism of DVT formation, the better our chances of finding safer ways to treat it. Just stopping inflammation alone will not inhibit thrombosis. You have to target the interaction between inflammation and thrombosis, which is why we think P-selectin or leukocyte-derived microparticles would make good therapeutic targets."

In addition to research designed to understand the complex relationship between inflammation and thrombosis, Wakefield also is conducting clinical studies to see whether microparticles or P-selectin could be used as a diagnostic marker for DVT formation in patients.

"Right now, the gold standard for diagnosis of DVT is ultrasound," Wakefield says. "We have other diagnostic tests, but none of them are accurate enough to use on their own. You have to combine them with a test such as ultrasound, which is expensive and labor-intensive. Better markers would allow us to detect the early stages of DVT development and intervene before problems develop."

The study was funded by the National Institutes of Health and Wyeth Research of Cambridge, Mass. In addition to Denisa Wagner, Ph.D., a professor of pathology and member of the Center for Blood Research at Harvard University, other research collaborators included Robert G. Schaub, Ph.D., assistant vice president of cardiovascular and metabolic diseases, Wyeth Research; Anjali Kumar, Ph.D., director of pharmacology, Critical Therapeutics in Cambridge, Mass.; U-M research associates Angela Hawley, Diana Farris, Shirley Wrobleski; and Porama Thanaporn, a U-M medical student.


Reference: The Journal of Vascular Surgery: 38 (5), pp.1075-1089 (November 2003)

Sally Pobojewski | EurekAlert!
Further information:
http://www2.med.umich.edu/prmc/media/relarch.cfm

More articles from Health and Medicine:

nachricht GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University

nachricht Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center

All articles from Health and Medicine >>>

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

Getting electrons to move in a semiconductor

25.04.2018 | Physics and Astronomy

Reconstructing what makes us tick

25.04.2018 | Physics and Astronomy

Cheap 3-D printer can produce self-folding materials

25.04.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>