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!
Infants later diagnosed with autism follow adults’ gaze, but seldom initiate joint attention
24.05.2019 | Schwedischer Forschungsrat - The Swedish Research Council
When wheels and heads are spinning - DFG research project on motion sickness in automated driving
22.05.2019 | Technische Universität Berlin
A new assessment of NASA's record of global temperatures revealed that the agency's estimate of Earth's long-term temperature rise in recent decades is accurate to within less than a tenth of a degree Fahrenheit, providing confidence that past and future research is correctly capturing rising surface temperatures.
The most complete assessment ever of statistical uncertainty within the GISS Surface Temperature Analysis (GISTEMP) data product shows that the annual values...
Physicists at the University of Basel are able to show for the first time how a single electron looks in an artificial atom. A newly developed method enables them to show the probability of an electron being present in a space. This allows improved control of electron spins, which could serve as the smallest information unit in a future quantum computer. The experiments were published in Physical Review Letters and the related theory in Physical Review B.
The spin of an electron is a promising candidate for use as the smallest information unit (qubit) of a quantum computer. Controlling and switching this spin or...
Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...
With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.
Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...
'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.
However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...
29.04.2019 | Event News
17.04.2019 | Event News
15.04.2019 | Event News
24.05.2019 | Physics and Astronomy
24.05.2019 | Medical Engineering
24.05.2019 | Life Sciences