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 Plasmonic biosensors enable development of new easy-to-use health tests
14.12.2017 | Aalto University

nachricht ASU scientists develop new, rapid pipeline for antimicrobials
14.12.2017 | Arizona State University

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: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Plasmonic biosensors enable development of new easy-to-use health tests

14.12.2017 | Health and Medicine

New type of smart windows use liquid to switch from clear to reflective

14.12.2017 | Physics and Astronomy

BigH1 -- The key histone for male fertility

14.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>