Navigation Links
Scientists identify novel way to prevent cardiac fibrosis
Date:4/22/2008

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 bodys 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 bodys 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 theres 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.


'/>"/>

Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

Related medicine news :

1. New prion protein discovered by Canadian scientists may offer insight into mad cow disease
2. Scientists Probe Sepsis Deadly Secrets
3. Scientists puzzled by severe allergic reaction to cancer drug in the middle Southern US
4. Scientists Develop Natural Protection for Stored Foods
5. Scientists detect presence of marburg virus in african fruit bats
6. Scientists Spot Brains Free Will Center
7. Scientists ID Likely Culprit in Popcorn Lung
8. Scientists explain how insulin secreting cells maintain their glucose sensitivity
9. Scripps Research scientists shed new light on how antibodies fight HIV
10. Scientists, physicians present latest findings in personalized cancer treatment and prevention
11. Scientists demonstate link between genetic variant and effectiveness of smoking cessation meds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:7/27/2017)... ... 2017 , ... Patients with missing teeth now have the ... from Dr. Alejandro Kovacs. Dr. Kovacs is a board-certified periodontist and prosthodontist who ... dental implants in Longview, TX. , During traditional dental implant ...
(Date:7/27/2017)... ... 27, 2017 , ... TransPanel Volume 4 is a collection of animating panel ... exclusive features transitions that contain between 2 and 6 animated panels. Change the direction ... menus. TransPanel Volume 4 makes editing easy in Final Cut Pro X. , TransPanel ...
(Date:7/27/2017)... Clara, CA (PRWEB) , ... July 27, 2017 ... ... announces the addition of a secure cloud-based polysomnography (PSG) distributed scoring solution to ... support accelerated diagnostics and sleep care management. The speed and functionality of scoring ...
(Date:7/27/2017)... ... 2017 , ... SSCI, a division of Albany Molecular Research, ... representing a milestone achievement. , As an industry-leading provider of ... served as expert and fact witnesses to assist our clients to perform infringement ...
(Date:7/27/2017)... ... ... Angeles leg of the US movie premier of the Man in the Camo Jacket will ... Davis Theater inside the Grammy Museum Located in downtown Los Angeles in the LA Live ... musician, Mike Peters (of The Alarm), his rise to fame, battle with cancer and inspiring ...
Breaking Medicine News(10 mins):
(Date:7/24/2017)... July 24, 2017  Diplomat Pharmacy, Inc. (NYSE: ... its second quarter 2017 operating results on Monday, August ... to follow at 5:00 p.m. ET. ... to a live broadcast of the conference call by ... participant code 51641230 approximately 15 minutes prior to the ...
(Date:7/20/2017)... 2017  Prime Therapeutics LLC (Prime) released this statement from ... today,s Institute for Clinical and Economic Review,s (ICER) public ... and value of abuse-deterrent formulations (ADF) of opioids. Prime was ... the meeting. "The ... to the use of abuse-deterrent formulations (ADF) in opioids in ...
(Date:7/14/2017)... VEGAS , July 13, 2017 It should ... United States is in the midst of a ... Control , since 1999, the number of overdose deaths from ... "resulting in over half a million dead from 2001 to ... codeine, oxycodone, and hydrocodone has similarly quadrupled, drawing a compelling ...
Breaking Medicine Technology: