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!
How the intestinal fungus Candida albicans shapes our immune system
22.02.2019 | Exzellenzcluster Präzisionsmedizin für chronische Entzündungserkrankungen
Stopping inflammation from becoming chronic
22.02.2019 | Friedrich-Schiller-Universität Jena
An international research team including astronomers from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has combined radio telescopes from five continents to prove the existence of a narrow stream of material, a so-called jet, emerging from the only gravitational wave event involving two neutron stars observed so far. With its high sensitivity and excellent performance, the 100-m radio telescope in Effelsberg played an important role in the observations.
In August 2017, two neutron stars were observed colliding, producing gravitational waves that were detected by the American LIGO and European Virgo detectors....
Up to now, OLEDs have been used exclusively as a novel lighting technology for use in luminaires and lamps. However, flexible organic technology can offer much more: as an active lighting surface, it can be combined with a wide variety of materials, not just to modify but to revolutionize the functionality and design of countless existing products. To exemplify this, the Fraunhofer FEP together with the company EMDE development of light GmbH will be presenting hybrid flexible OLEDs integrated into textile designs within the EU-funded project PI-SCALE for the first time at LOPEC (March 19-21, 2019 in Munich, Germany) as examples of some of the many possible applications.
The Fraunhofer FEP, a provider of research and development services in the field of organic electronics, has long been involved in the development of...
For the first time, an international team of scientists based in Regensburg, Germany, has recorded the orbitals of single molecules in different charge states in a novel type of microscopy. The research findings are published under the title “Mapping orbital changes upon electron transfer with tunneling microscopy on insulators” in the prestigious journal “Nature”.
The building blocks of matter surrounding us are atoms and molecules. The properties of that matter, however, are often not set by these building blocks...
Scientists at the University of Konstanz identify fierce competition between the human immune system and bacterial pathogens
Cell biologists from the University of Konstanz shed light on a recent evolutionary process in the human immune system and publish their findings in the...
Laser physicists have taken snapshots of carbon molecules C₆₀ showing how they transform in intense infrared light
When carbon molecules C₆₀ are exposed to an intense infrared light, they change their ball-like structure to a more elongated version. This has now been...
11.02.2019 | Event News
30.01.2019 | Event News
16.01.2019 | Event News
22.02.2019 | Life Sciences
22.02.2019 | Health and Medicine
22.02.2019 | Life Sciences