Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study links inflammation and calcium signaling in heart attack

10.03.2009
Research reveals new role for immune system pathway in post-heart attack inflammation

A new study led by University of Iowa researchers has found an unexpected new link between this inflammation in heart muscle following a heart attack and a previously known enzyme called calcium/calmodulin-dependent protein kinase II or CaM kinase II. The findings also reveal the involvement of an immune system gene -- complement factor B -- that has been implicated in other inflammatory diseases.

The study, published online March 9 in the Journal of Clinical Investigation, suggests that CaM kinase II inhibition could be a therapeutic target in heart disease, but by previously unknown pathways.

CaM kinase II is a pivotal enzyme that registers changes in calcium levels and oxidative stress and translates these signals into cellular effects, including changes in heart rate, cell proliferation and cell death. CaM kinase II also regulates gene expression -- which genes are turned on or off at any given time. Inhibition of CaM kinase II in mice protects the animals' hearts against some of the damaging effects of a heart attack.

To better understand how CaM kinase II pathways are involved in damage caused by heart attack, the UI researchers investigated the effect of CaM kinase II activity on gene expression during a heart attack. The study's lead author was Madhu Singh, Ph.D., UI research scientist, and the senior author was Mark Anderson, M.D., Ph.D., professor of internal medicine and molecular physiology and biophysics at the UI Roy J. and Lucille A. Carver College of Medicine and director of the Division of Cardiovascular Medicine.

"We used a mouse model in which CaM kinase II is inhibited in heart muscle cells. These mice are protected from many of the ill effects of heart attack," Singh said. "We compared a large number of genes that were expressed in the protected mice compared to the non-protected control mice. A particularly interesting finding was that a cluster of inflammatory genes was differently expressed depending on whether CaM kinase II was active or inhibited."

Specifically, the research showed that heart attack triggered increased expression of a set of pro-inflammatory genes, and inhibition of CaM kinase II substantially reduced this effect.

The team focused on the most highly regulated of these inflammatory genes -- complement factor B. The protein produced by this gene is involved in the innate immune system called the alternative complement pathway.

The team found that complement factor B protein is synthesized in heart muscle cells as part of an autoimmune response to heart attack and that complement factor B protein participates in the formation of the so-called membrane attack complex, which punctures holes in heart cell membranes.

"It was very surprising that heart muscle cells express complement factor B, an immune system protein, because traditionally these cells are known for their contraction function, which supports heart pumping, not as part of the immune response to injury," Singh said.

Complement factors are part of the first line of defense against pathogens. When complement pathways are triggered, a biological cascade is set in motion that results in the formation of a membrane attack complex – a group of proteins that can literally punch holes in the cell membrane of an invading microbe or an injured cell.

The UI team showed that the complement factor B produced in heart muscle cells helped form membrane attack complexes that were able to puncture the cell membranes of heart muscle cells in a petri dish. In addition, the researchers found that genetically engineered mice that did not express functional complement factor B were partly protected from heart attack -- showing reduced mortality and heart damage.

"Clearly, if this immune system response is induced during heart attack injury, it might amplify heart damage by poking holes in the cell membrane," Singh said. "Not only is the heart trying to recover from the injury induced by the heart attack, but it also has to deal with the consequences of the induced activity of the complement pathway, which is attacking the cell membranes.

"If we can reduce the extra burden on the heart by some means of inhibiting this activity, then clinically that might be useful, he added.

"These findings show a previously unanticipated connection between CaM kinase II activity and inflammation in heart muscle and show that this connection drives maladaptive responses to heart attack," said Anderson, who also holds the Potter-Lambert Chair in Cardiology. "By understanding these CaM kinase II signaling mechanisms that occur inside the cell we might arrive at new and better drug targets that act more specifically to treat a variety of heart problems."

Jennifer Brown | EurekAlert!
Further information:
http://www.uiowa.edu

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Gold shines through properties of nano biosensors

17.08.2017 | Physics and Astronomy

Greenland ice flow likely to speed up: New data assert glaciers move over sediment, which gets more slippery as it gets wetter

17.08.2017 | Earth Sciences

Mars 2020 mission to use smart methods to seek signs of past life

17.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>