Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Beyond lipids: understanding the mechanics of atherosclerosis

13.07.2006
Atherosclerotic narrowing and hardening of coronary arteries typically appear first at vessel branches, and a study in the October issue of Cellular Signalling reports that the type of mechanical stretching found at those branches activates a cellular protein known to damage cells. The report is the first to link mechanical forces with structural and biochemical changes in blood vessel cells that could explain why atherosclerotic lesions form preferentially at branches of coronary arteries.

The findings, which are currently available online at the journal’s Website, were reported by a team of scientists at the University of California, San Diego as part of an ongoing effort to understand how mechanical forces affect the health of cells that line arteries.

The cellular protein in question is called JNK, which is short for c-jun N-terminal kinase. The protein is a key barometer of outside stresses on a variety of cell types. Researchers are examining the role of JNK in many diseases because it regulates the expression of genes involved in programmed cell death, tumor genesis, and other stress responses.

Atherosclerosis, the collection of deposits such as cholesterol along artery walls, accounts for nearly 75 percent of deaths from cardiovascular disease. Most drugs to treat atherosclerosis influence the levels of cholesterol and other lipids in the blood, but the UCSD researchers suspect that understanding the role of mechanical forces acting on blood vessel cells may help to design better approaches to treatment.

“We’ve known for decades that atherosclerotic lesions develop preferentially at vessel branches rather than along unbranched vessels, but we’ve not been able to identify the biochemical events that trigger formation of the lesions,” said Shu Chien, director of the Whitaker Institute of Biomedical Engineering at UCSD. “We now have identified a possible smoking gun: activation of JNK, which is dependent on the directionality of blood vessel stretching.”

Chien, research scientist Shunichi Usami, and post-doctoral fellow Roland Kaunas, now an assistant professor of biomedical engineering at Texas A&M University,isolated endothelial cells from the bovine aorta and grew them in culture flasks. They seeded the cells onto silicone rubber membranes that had been coated with a protein that allowed the cells to attach the way they do to underlying blood vessel tissue in the body.They then stretched the cells 10 percent of their length 60 times per minute to simulate the rhythmic flexing of an artery in response to heart beats.

Cells that were stretched back and forth along one axis exhibited a healthy response: the level of JNK rose and quickly returned to basal levels as the cells also produced intracellular actin fibers that were aligned perpendicular to the axis of stretching. However, when the researchers stretched cells in two directions simultaneously, they noted an unhealthy response: actin fibers oriented randomly and JNK concentrations rose to higher levels and remain elevated.

“We’re continually amazed at how quickly these cells can reorient these stress fibers when we change the direction of stretch,” said Chien. “At the same time, the actin cytoskeleton of endothelial cells is somehow playing a key role in activating and deactivating JNK.”

The tubular geometry of the straight part of arteries ensures that the cyclical rise and fall of blood pressure results in uniaxial stretch of arteries. However, the more complex geometry of artery branches promotes an unhealthy stretching of the blood vessel along more than one axis.

A second mechanical force, the so-called shear force of blood flowing through vessels, also influences the orientation of stress fibers in endothelial cells. A laminar flow of blood prompts stress fibers to orient in the healthy direction, while disturbed and low blood flows caused stress fibers to form in an unhealthy, random orientation. Chien’s group is now working to understand how both stretching and shear forces influence JNK activation.

“We still need to limit the amount of cholesterol in our diet, especially the low-density lipoprotein, or bad cholesterol,” said Chien. “But our new understanding of how mechanical forces affect JNK will eventually help us gain better understanding of the mechanism underlying the focal localization of atherosclerotic lesions and design better approaches to treat this important disease state.”

Roland Kaunas, Shunichi Usami, and Shu Chien, "Regulation of stretch-induced JNK activation by stress fiber orientation" (2006). Cellular Signalling. doi:10.1016/j.cellsig.2006.02.008

Rex Graham | EurekAlert!
Further information:
http://www.ucsd.edu
http://www.jacobsschool.ucsd.edu/news_events/releases/release.sfe?id=554

More articles from Health and Medicine:

nachricht Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>