Featured Research

from universities, journals, and other organizations

Atherosclerosis: The Janus-like nature of JAM-A

Date:
September 30, 2013
Source:
Ludwig-Maximilians-Universitaet Muenchen (LMU)
Summary:
A new study sheds light on the role of the adhesion molecule JAM-A in the recruitment of immune cells to the inner layer of arteries – which promotes the development of atherosclerosis.

A new study by Ludwig-Maximilians-Universitaet (LMU) in Munich researchers led by Christian Weber sheds light on the role of the adhesion molecule JAM-A in the recruitment of immune cells to the inner layer of arteries -- which promotes the development of atherosclerosis.

Multiphoton microscopy makes it possible to image the vessel wall (blue: collagen) and inner lining of an artery that has been subjected to atherosclerosis-promoting conditions. Staining for endothelial cells (red) and JAM-A (green) reveals the localization of JAM-A at the cell junctions and the first signs of its redistribution to the cell surface. Areas of overlap with the endothelial cell marker gives rise to the intense yellow signal.

Atherosclerosis is characterized by the formation of fatty "plaques" on the inner lining of the arteries, and is facilitated by high levels of fat in the diet. These "plaques" constrict the vessel, restrict the flow of blood, and may precipitate strokes and heart attacks. Monocytes, which belong to the immune system and help to defend the body against pathogens, also play a central role in the development of atherosclerotic lesions. In regions of the vasculature where the normal pattern of blood flow is disturbed, monocytes can penetrate the vessel wall and release signal molecules into the underlying tissue, which attract other immune cells to the site. The resulting inflammatory reaction then leads to the build-up of plaques.

Professor Christian Weber of the Institute for Prophylaxis and Epidemiology of Cardiovascular Diseases at LMU studies the molecular processes that facilitate the migration of these cells between the cells of the vessel wall. In the latest issue of the journal Circulation, he and his team report the results of an investigation carried out in collaboration with colleagues based at Maastricht University, which was designed to elucidate the role of an adhesion molecule called JAM-A in the development of atherosclerosis.

Molecular multitasking JAM-A is of interest because it is expressed both in the blood-vessel wall and in white blood cells, including monocytes. The protein harbours a variety of binding sites, and can interact with itself and several other binding partners. The acronym stands for "Junctional Adhesion Molecule-A," and refers to its primary function in mediating cell-cell contacts. In essence, it serves as a molecular zipper between cells. In the new study, Weber and his colleagues have looked at the effects of the targeted reduction of JAM-A levels in specific cell types.

The walls of veins and arteries are made up of a monolayer of so-called endothelial cells, which are held together by cell-cell junctions that include JAM-A. At sites, where laminar blood flow is perturbed, JAM-A is redistributed away from the intercellular junctions to the cell surface. This promotes attachment of monocytes and allows them to migrate between the endothelial cells into the tissues. Weber and his team have now shown that, when the levels of JAM-A in endothelial cells are reduced, fewer monocytes get through, and fewer lesions are formed.

This might suggest that pharmacological blockade of JAM-A could reduce the incidence of atherosclerotic lesions, but there is a catch. For when the molecule is deleted from monocytes, the cells get trapped as they migrate through the endothelial cell layer. This results in local damage to the vessel wall, and enhances the formation of plaques.

"In order to develop anti-atherosclerotic drugs that target JAM-A, one must take the whole repertoire of its interactions into consideration," says Christian Weber. He is now trying to identify the binding site responsible for the plaque-promoting effects of the molecule. "A drug that specifically blocked only that site could have a protective effect on the vasculature without provoking deleterious side-effects," he says.


Story Source:

The above story is based on materials provided by Ludwig-Maximilians-Universitaet Muenchen (LMU). Note: Materials may be edited for content and length.


Journal Reference:

  1. Schmitt MM, Megens RT, Zernecke A, Bidzhekov K, van den Akker NM, Rademakers T, van Zandvoort MA, Hackeng TM, Koenen RR, Weber C. Endothelial JAM-A Guides Monocytes into Flow-Dependent Predilection Sites of Atherosclerosis. Circulation, September 2013

Cite This Page:

Ludwig-Maximilians-Universitaet Muenchen (LMU). "Atherosclerosis: The Janus-like nature of JAM-A." ScienceDaily. ScienceDaily, 30 September 2013. <www.sciencedaily.com/releases/2013/09/130930093750.htm>.
Ludwig-Maximilians-Universitaet Muenchen (LMU). (2013, September 30). Atherosclerosis: The Janus-like nature of JAM-A. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2013/09/130930093750.htm
Ludwig-Maximilians-Universitaet Muenchen (LMU). "Atherosclerosis: The Janus-like nature of JAM-A." ScienceDaily. www.sciencedaily.com/releases/2013/09/130930093750.htm (accessed October 22, 2014).

Share This



More Plants & Animals News

Wednesday, October 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Working Mother DIY: Pumpkin Pom-Pom

Working Mother DIY: Pumpkin Pom-Pom

Working Mother (Oct. 22, 2014) How to make a pumpkin pom-pom. Video provided by Working Mother
Powered by NewsLook.com
San Diego Zoo's White Rhinos Provide Hope for the Critically Endangered Species

San Diego Zoo's White Rhinos Provide Hope for the Critically Endangered Species

Reuters - Light News Video Online (Oct. 22, 2014) The pair of rare white northern rhinos bring hope for their species as only six remain in the world. Elly Park reports. Video provided by Reuters
Powered by NewsLook.com
Raw: Bear Cub Strolls Through Oregon Drug Store

Raw: Bear Cub Strolls Through Oregon Drug Store

AP (Oct. 22, 2014) Shoppers at an Oregon drug store were surprised by a bear cub scurrying down the aisles this past weekend. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Family Pleads for Pet Pig to Stay at Home

Family Pleads for Pet Pig to Stay at Home

AP (Oct. 22, 2014) The Johnson family lost their battle with the Chesterfield County, Virginia Planning Commission to allow Tucker, their pet pig, to stay in their home, but refuse to let the board keep Tucker away. (Oct. 22) 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:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

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