Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New cellular pathway helps explain how inflammation leads to artery disease

22.06.2018

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.


Atherosclerotic lesions appear in red in this image of a mouse aorta.

Credit: Cedars-Sinai

"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:

  • To make its way out of the immune system cell, interleukin-1 beta can also use the same chemical channels that are used by cholesterol to exit the cell. The result is a "traffic rush" on those channels that blocks the exit of artery-damaging cholesterol and causes it to accumulate in the cell.
  • Once it is released by the cell into the body, interleukin-1 beta suppresses a chemical receptor that enables niacin, or Vitamin B3, to be used in the body. This action is harmful because niacin works by removing cholesterol from cells in the artery walls. When niacin is blocked, cholesterol can accumulate in the walls.
  • The suppression of the niacin receptor has another negative effect: It reduces the number of chemical channels that cholesterol uses to exit the immune system cell, causing more cholesterol to be trapped inside. That is because the niacin receptor, besides enabling niacin, also increases these channels as part of its normal function.

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.

Media Contact

Jane Engle
Jane.Engle@cshs.org
310-248-8545

 @cedarssinai

http://www.csmc.edu 

Jane Engle | EurekAlert!
Further information:
http://dx.doi.org/10.1016/j.cmet.2018.05.027

More articles from Life Sciences:

nachricht In depression the brain region for stress control is larger
20.09.2018 | Max-Planck-Institut für Kognitions- und Neurowissenschaften

nachricht Interfacial engineering core@shell nanoparticles for active and selective direct H2O2 generation
19.09.2018 | Science China Press

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Scientists present new observations to understand the phase transition in quantum chromodynamics

The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.

This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.

Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...

Im Focus: Patented nanostructure for solar cells: Rough optics, smooth surface

Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.

"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...

Im Focus: New soft coral species discovered in Panama

A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.

Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...

Im Focus: New devices based on rust could reduce excess heat in computers

Physicists explore long-distance information transmission in antiferromagnetic iron oxide

Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.

Im Focus: Finding Nemo's genes

An international team of researchers has mapped Nemo's genome

An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

One of the world’s most prominent strategic forums for global health held in Berlin in October 2018

03.09.2018 | Event News

4th Intelligent Materials - European Symposium on Intelligent Materials

27.08.2018 | Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

 
Latest News

Glacial engineering could limit sea-level rise, if we get our emissions under control

20.09.2018 | Earth Sciences

Warning against hubris in CO2 removal

20.09.2018 | Earth Sciences

Halfway mark for NOEMA, the super-telescope under construction

20.09.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>