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!
NTU scientists build new ultrasound device using 3-D printing technology
07.12.2016 | Nanyang Technological University
How to turn white fat brown
07.12.2016 | University of Pennsylvania School of Medicine
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
07.12.2016 | Health and Medicine
07.12.2016 | Life Sciences
07.12.2016 | Health and Medicine