Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists identify novel way to prevent cardiac fibrosis

24.04.2008
In a study that points to a new strategy for preventing or possibly reversing fibrosis – the scarring that can lead to organ and tissue damage – researchers at the University of California, San Diego School of Medicine have determined that a molecule called Epac (Exchange protein activated by cAMP1), plays a key role in integrating the body’s pro- and anti-fibrotic response.

The research will be published in the online edition of the Proceedings of the National Academy of Science (PNAS) the week of April 21.

Inflammation is the body’s response to injury in tissues, prompting healing that leads to scars, whether on the skin, or in organs such as the heart, liver or lungs. Such scarring has beneficial properties, but there’s also the risk of excessive scarring, or tissue fibrosis, that can lead to organ damage and loss of function.

The UC San Diego researchers looked at cardiac fibrosis, which can occur in patients who have suffered an infection of the heart muscle or a heart attack. Such fibrosis causes the heart to stiffen so that it cannot adequately fill with blood and then empty itself, a condition known as diastolic dysfunction.

“An old heart is a stiff heart and some injured hearts are stiff as well,” said Paul A. Insel, M.D., UCSD professor of pharmacology and medicine, and principal investigator of the study. “Much of the decrease in cardiovascular function that occurs with aging or, in some patients after a heart attack, can be explained by fibrosis. We wondered: What is responsible for excessive fibrosis" Is there a way to decrease or possibly reverse it"”

It was previously known that a messenger molecule inside of cells, called cAMP, can block fibrosis in the heart. Insel and colleagues explored the mechanism leading to the anti-fibrotic effect, and discovered that the Epac molecule mediates cAMP actions that are involved in cardiac fibrosis. Epac also helps regulate other proteins that contribute to cell death, division, migration and motility.

“We found that Epac activation exerts a very important impact on the function of fibroblasts, the cells responsible for making and secreting collagen and thus for producing tissue fibrosis,” said Insel. “Most exciting was our discovery that multiple agents that promote fibrosis decrease the expression and activation of Epac in fibroblasts from several different tissues – not only in the heart but also in lung, liver and skin.”

The researchers found decreased Epac expression in regions near the site of heart attacks in rats and mice. In addition, they found that by increasing Epac expression, they were able to block the ability of agents to promote fibrosis.

Because increases in cAMP levels can decrease the function of fibroblasts after cell injury, stimulation of the cAMP signaling pathway is a potential way to blunt fibrosis. Increases in Epac expression may provide a novel way to do this, especially in cardiac fibroblasts, Insel added. To test this possibility, the scientists treated fibroblast cells in culture in ways that altered Epac expression, increasing Epac expression using an adenoviral construct.

“Using this strategy to overexpress Epac, we produced an anti-fibrotic effect, thereby inhibiting the synthesis of collagen” said Insel. “Other experiments showed that decreasing Epac expression favored fibrosis; in other words, were pro-fibrotic. Overall, the results show the central role of Epac in determining pro-fibrotic and anti-fibrotic response.”

Debra Kain | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Health and Medicine:

nachricht MRI contrast agent locates and distinguishes aggressive from slow-growing breast cancer
25.09.2017 | Case Western Reserve University

nachricht Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

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: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

An international team of physicists a coherent amplification effect in laser excited dielectrics

25.09.2017 | Physics and Astronomy

LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

25.09.2017 | Trade Fair News

Highest-energy cosmic rays have extragalactic origin

25.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>