Featured Research

from universities, journals, and other organizations

New light shed on how blood clots form

Date:
June 14, 2011
Source:
Scripps Research Institute
Summary:
Scientists have discovered new elements of the blood clot-formation process. The findings could lead to better drugs for preventing heart attacks and other clot-related conditions.

Scripps Research Institute scientists have discovered new elements of the blood clot-formation process. The findings could lead to better drugs for preventing heart attacks and other clot-related conditions.

Related Articles


The work, which was published by the Journal of Clinical Investigation in an advance, online edition June 13, 2011, helps to establish a new model of clot formation.

According to the old model, an injury to the wall of blood vessels causes smooth muscle cells to expose a clot-organizing protein called tissue factor. "In the emerging new model, tissue factor exists on the surfaces of these smooth muscle cells, as well as on circulating immune cells, but in an inactive state," said Scripps Research Professor Wolfram Ruf. "In this study, we've shown that cell-surface receptor P2X7, which was known to promote inflammation when stimulated, also plays a major role in the clot-forming process by activating tissue factor."

An Intriguing Target

To better understand clot formation, Ruf and his colleagues performed a set of experiments on cultured mouse cells and transgenic mouse models. The team's investigation began with the P2X7 receptor, because of its known role in the inflammatory response that can lead to excessive clotting in sepsis, a severe illness in which the bloodstream is overwhelmed by bacteria.

Normally, when cells are damaged, they release large quantities of energy-storage molecules known as adenosine triphosphate (ATP). Previous research had hinted that when this freed ATP encounters passing immune cells, it serves as a damage signal, stimulating the immune cells' P2X7 receptors and causing the release of "microparticles" exposing the clot-promoting tissue factor. The new study showed that ATP can affect P2X7 receptors on both immune cells and smooth muscle cells.

To confirm the significance of the P2X7 receptor in the clot-forming process, the team bred transgenic mice that lacked functional P2X7 receptors, and found that these P2X7-knockout mice failed to form stable arterial blood clots when the vessel wall was exposed to a clot-inducing substance. Importantly, these mice did not suffer from uncontrollable bleeding. "This suggests that clot-preventing drugs targeting the P2X7 pathway might not have unacceptable side effects," said Ruf.

In the cell experiments, the team found that the cascade of molecular events following P2X7 stimulation alters the activity of a thiol-targeting enzyme known as protein disulfide isomerase (PDI), which Ruf's previous studies had implicated as a possible activator of tissue factor. In the new study, the scientists demonstrated the importance of PDI in this process by showing that they could block clot formation in normal mice with anti-PDI antibodies.

Targeting the top of the clot-formation pathway by blocking the P2X7 receptor might have even broader beneficial effects, since the activation of this receptor occurs in a number of inflammatory disorders.

"Cardiovascular disease and heart attacks are caused by chronic inflammation as well as clot formation," said Ruf, "so possibly P2X7 is a major explanation for the link between inflammation and thrombosis, as well as a good target for preventing these conditions."


Story Source:

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


Journal Reference:

  1. Christian Furlan-Freguia, Patrizia Marchese, Andrαs Gruber, Zaverio M. Ruggeri, Wolfram Ruf. P2X7 receptor signaling contributes to tissue factor–dependent thrombosis in mice. Journal of Clinical Investigation, 2011; DOI: 10.1172/JCI46129

Cite This Page:

Scripps Research Institute. "New light shed on how blood clots form." ScienceDaily. ScienceDaily, 14 June 2011. <www.sciencedaily.com/releases/2011/06/110613162112.htm>.
Scripps Research Institute. (2011, June 14). New light shed on how blood clots form. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2011/06/110613162112.htm
Scripps Research Institute. "New light shed on how blood clots form." ScienceDaily. www.sciencedaily.com/releases/2011/06/110613162112.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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