Findings of Cedars-Sinai-led study suggest ways to improve therapies for heart attacks and stroke
Investigators have identified a new cellular pathway that may help explain how arterial inflammation develops into atherosclerosis--deposits of cholesterol, fats and other substances that create plaque, clog arteries and promote heart attacks and stroke. The findings could lead to improved therapies for atherosclerosis, a leading cause of death worldwide.
"We have known for decades that atherosclerosis is a disease of chronic inflammation that ultimately results in the scarring of arteries and tissue damage," said Moshe Arditi, MD, director of the Infectious and Immunologic Disorders Translational Research Center in the Department of Biomedical Sciences at Cedars-Sinai. "But the ongoing stimulus for this inflammation has been unclear."
A study published today in the journal Cell Metabolism sheds light on this mystery by using a bacterial infection to reveal a cascade of cellular events that can lead to inflammation and atherosclerosis. Arditi is the co-senior author and the lead author of the study, which was led by investigators at Cedars-Sinai.
Investigators focused on interleukin-1 beta, a type of protein that is assembled and released by immune system cells in response to infection and injury, including tissue damage caused by atherosclerosis. While interleukin-1 beta helps rally the immune system against these threats, it also can cause chronic inflammation. The study team wanted to understand how the interleukin-1 beta pathway might promote atherosclerosis.
Using laboratory mice bearing a bacterial infection, along with human cells cultured in a petri dish, the team discovered that several harmful processes related to interleukin-1 beta can lead to buildup of cholesterol in the arteries:
Arditi said these discoveries are especially significant because drugs that inhibit interleukin-1 beta have shown promise in combatting atherosclerosis and heart disease. A major clinical trial, led by another research institution and published last year, reported that administering one such drug to patients who had a prior heart attack reduced inflammation and lowered the risk of another cardiovascular event.
The Cedars-Sinai study raises the possibility that by using drugs to block the initial production of interleukin-1 beta, rather than just neutralizing it, a stronger positive effect could be obtained for these patients, said Arditi, professor of Pediatrics and Biomedical Sciences.
Prediman K. Shah, MD, director of the Atherosclerosis Prevention and Management Center at Cedars-Sinai, noted that a drug, colchicine, already exists that blocks interleukin-1 beta production, but it is FDA-approved only to treat gout and Mediterranean fever. Two clinical trials are underway elsewhere to evaluate the drug's potential for treating atherosclerosis and preventing heart attacks.
In addition, Shah, a professor of Medicine who was not involved in the Cedars-Sinai study, said, "A very intriguing aspect of these findings is that they could prompt a re-examination of niacin therapy for atherosclerosis and heart disease." He explained that physicians long used niacin to treat atherosclerosis until the 1980s, when statin drugs were shown to be more effective at reducing cholesterol and cardiovascular risk.
The newly released study suggests that combining niacin with an interleukin-1 beta inhibitor might enhance niacin therapy by making niacin more available to the body, Arditi said.
Besides Arditi, the other co-senior author of the new study is Shuang Chen, MD, PhD, assistant professor of Pediatrics and Biomedical Sciences at Cedars-Sinai. The first authors are Gantsetseg Tumurkhuu, PhD, a postdoctoral scientist in Arditi's lab, and Jargalsaikhan Dagvadorj, PhD, a research scientist in that lab.
Research reported in this publication was supported by the National Institutes of Health under award numbers HL111483, AI105845 and HL066436.
Jane Engle | EurekAlert!
Machine learning microscope adapts lighting to improve diagnosis
20.11.2019 | Duke University
The neocortex is critical for learning and memory
20.11.2019 | Max-Planck-Institut für Hirnforschung
Conventional light microscopes cannot distinguish structures when they are separated by a distance smaller than, roughly, the wavelength of light. Superresolution microscopy, developed since the 1980s, lifts this limitation, using fluorescent moieties. Scientists at the Max Planck Institute for Polymer Research have now discovered that graphene nano-molecules can be used to improve this microscopy technique. These graphene nano-molecules offer a number of substantial advantages over the materials previously used, making superresolution microscopy even more versatile.
Microscopy is an important investigation method, in physics, biology, medicine, and many other sciences. However, it has one disadvantage: its resolution is...
Nanooptical traps are a promising building block for quantum technologies. Austrian and German scientists have now removed an important obstacle to their practical use. They were able to show that a special form of mechanical vibration heats trapped particles in a very short time and knocks them out of the trap.
By controlling individual atoms, quantum properties can be investigated and made usable for technological applications. For about ten years, physicists have...
An international team of scientists, including three researchers from New Jersey Institute of Technology (NJIT), has shed new light on one of the central mysteries of solar physics: how energy from the Sun is transferred to the star's upper atmosphere, heating it to 1 million degrees Fahrenheit and higher in some regions, temperatures that are vastly hotter than the Sun's surface.
With new images from NJIT's Big Bear Solar Observatory (BBSO), the researchers have revealed in groundbreaking, granular detail what appears to be a likely...
The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM in Dresden has succeeded in using Selective Electron Beam Melting (SEBM) to...
Carbon nanotubes (CNTs) are valuable for a wide variety of applications. Made of graphene sheets rolled into tubes 10,000 times smaller than a human hair, CNTs have an exceptional strength-to-mass ratio and excellent thermal and electrical properties. These features make them ideal for a range of applications, including supercapacitors, interconnects, adhesives, particle trapping and structural color.
New research reveals even more potential for CNTs: as a coating, they can both repel and hold water in place, a useful property for applications like printing,...
15.11.2019 | Event News
15.11.2019 | Event News
05.11.2019 | Event News
20.11.2019 | Life Sciences
20.11.2019 | Physics and Astronomy
20.11.2019 | Health and Medicine