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:12/2/2016)... ... December 02, 2016 , ... The annual time frame to change Medicare health ... is ending December 7th. Currently-enrolled Medicare beneficiaries who are looking to switch from their ... D) need to make changes during this period order for their new policy to ...
(Date:12/2/2016)... (PRWEB) , ... December 02, 2016 , ... More than ... and while 84 percent of parents report speaking with their child about sex related ... sexually transmitted diseases. , Mediaplanet is proud to announce the launch of its second ...
(Date:12/2/2016)... ... December 02, 2016 , ... Sourced from the Isbre Springs beneath the 5,000 ... unmatched natural purity of just 6 ppm TDS (Total Dissolved Solids) in addition to ... been available in several ShopRite and FoodTown stores in NJ and received rave comments ...
(Date:12/2/2016)... Miami, FL (PRWEB) , ... December 02, 2016 ... ... over 5,100 hot meals to needy individuals and families from eight different sites ... Florida on Thanksgiving Day. Over 1,000 volunteers worked very hard on Thanksgiving morning ...
(Date:11/30/2016)... , ... November 30, 2016 , ... ... they now offer a comprehensive in-house dental plan for all patients. Understanding that ... a plan that gives patients a number of perks, including discounts on many ...
Breaking Medicine News(10 mins):
(Date:12/2/2016)... YORK , December 2, 2016 ... Braces & Support) is Expected to Gain a Significant Market ... to Orthopedic Ailments  ... , According to ... Study on Medical Implants Sterile Packaging: Clamshell Product Type Segment ...
(Date:12/2/2016)... On Thursday, the NASDAQ Composite and ... the Dow Jones Industrial Average managed to stay in green. ... which prompted Stock-callers this morning to look at the performances ... NUVA ), Smith & Nephew PLC (NYSE: SNN ... Cesca Therapeutics Inc. (NASDAQ: KOOL ). You can ...
(Date:12/2/2016)... -- The concept of rare diseases and the idea that ... has been taking shape in Europe ... initiatives related to orphan medicinal products have been emerging at ... states individually. Many member states in the EU have led ... medicinal products, the result of which took the shape of ...
Breaking Medicine Technology: