Featured Research

from universities, journals, and other organizations

How Life-threatening Blood Clots Take Hold

Date:
April 17, 2009
Source:
Cell Press
Summary:
When plaques coating blood vessel walls rupture and expose collagen, platelets spring into action to form a blood clot at the damaged site. Now scientists reveal how those life-threatening clots -- a leading cause of death in the United States, Europe and other industrialized countries -- get an early grip. The discovery might offer a new way to fight clot formation before it can even begin, according to the researchers.

When plaques coating blood vessel walls rupture and expose collagen, platelets spring into action to form a blood clot at the damaged site. Now, a new report in the April 17th issue of the journal Cell reveals how those life-threatening clots—a leading cause of death in the United States, Europe and other industrialized countries--get an early grip. The discovery might offer a new way to fight clot formation before it can even begin, according to the researchers.

"Compared to other diseases, blood clotting has been very well understood," said Athan Kuliopulos of Tufts Medical Center and Tufts University School of Medicine. Nevertheless, he continued, many people still suffer from heart attacks, ischemic stroke and death as a result of clot formation.

"Drugs designed to inhibit clots through known pathways are widely used by millions. They work well, but not perfectly. There is still an unmet need." Those drugs include aspirin and the so-called thienopyridines, including Clopidogrel (trade name Plavix).

Scientists have known that a protein called thrombin plays an important role in clot formation as a potent activator of platelets. It also cuts fibrinogen into fibrin, a fibrous protein that works together with platelets to form a clot.

But thrombin isn't the whole story. Enzymes known as matrix metalloproteases have recently emerged as important players in platelet function and the biology of blood vessels. Two of those enzymes, MMP-1 and MMP-2 can actually encourage platelet activation, according to earlier studies, although the means were unknown. In cancer cells too, MMP-1 activates a receptor known as PAR1 – the same receptor that is also responsible for receiving the thrombin signal on human platelets.

"There is abundant proMMP-1 coating platelets," Kuliopulos said. "We thought maybe it was on the outside waiting to be activated by something. Maybe it could be involved in an early event in blood clotting, before thrombin is around."

Indeed, Kuliopulos' team has now connected those dots. They show that exposure of platelets to collagen activates MMP-1, which in turn directly cut PAR1 on the surface of platelets. Collagen is the first thing a platelet "sees" when a blood vessel ruptures or is cut.

The MMP-1-PAR1 pathway activates another set of molecular players known to be involved in early clot formation, he said. Those activated platelets change their shape, sending out spikes and membrane sheets. "Within seconds, they become more sticky," adhering to the vessel surface and then other platelets.

Moreover, they show that treatments that block the MMP1-PAR1 pathway prevent blood clots from forming in the presence of collagen, suggesting that drugs targeting this metalloprotease-receptor system could offer a new way to treat patients with acute coronary syndromes.

According to the new results, PAR1 inhibitors already being tested in clinical trials might have an added benefit, Kuliopulos said. It's also possible they might work a little too well, since there is a careful balance between the risk of dangerous blood clots and the risk of bleeding. "An MMP-1 inhibitor might be better tolerated," he said.

The researchers include Vishal Trivedi, Adrienne Boire, Boris Tchernychev, Nicole C. Kaneider, Andrew J. Leger, Katie O'Callaghan, Lidija Covic, and Athan Kuliopulos, of Tufts University School of Medicine, Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "How Life-threatening Blood Clots Take Hold." ScienceDaily. ScienceDaily, 17 April 2009. <www.sciencedaily.com/releases/2009/04/090416125201.htm>.
Cell Press. (2009, April 17). How Life-threatening Blood Clots Take Hold. ScienceDaily. Retrieved April 19, 2014 from www.sciencedaily.com/releases/2009/04/090416125201.htm
Cell Press. "How Life-threatening Blood Clots Take Hold." ScienceDaily. www.sciencedaily.com/releases/2009/04/090416125201.htm (accessed April 19, 2014).

Share This



More Health & Medicine News

Saturday, April 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com
Obama: 8 Million Healthcare Signups

Obama: 8 Million Healthcare Signups

AP (Apr. 17, 2014) President Barack Obama gave a briefing Thursday announcing 8 million people have signed up under the Affordable Care Act. He blasted continued Republican efforts to repeal the law. (April 17) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins