New target for heart failure therapy identified

March 16, 2009

A novel signaling pathway plays a significant role in the production of aldosterone, a hormone that promotes heart failure after a myocardial infarction, according to a study conducted by Thomas Jefferson University researchers.

The findings, which will be published online this week in , show that aldosterone production is mediated by a protein called beta-arrestin-1. Beta-arrestin-1 binds to angiotensin II receptors when they are activated by angiotensin II.

Aldosterone is secreted by the adrenal cortex. Its levels are elevated in chronic , and its presence contributes to morbidity and mortality of the disease. It contributes to heart failure progression and diminished cardiac function after .

The production of aldosterone was previously thought to be solely the result of the activation of G-proteins, which are also activated when angiotensin II binds to its receptors, according to Anastasios Lymperopoulos, Ph.D., a Post-Doctoral Research Fellow in the Center for Translational Medicine and the George Zallie and Family Laboratory for Cardiovascular Gene Therapy at Jefferson Medical College of Thomas Jefferson University.

"The bottom line is that in order to effectively suppress aldosterone production, you need to inhibit beta-arrestin-1 in addition to inhibiting G-proteins," said Dr. Lymperopoulos, who is the lead author of the study.

All the drugs currently available for suppression of aldosterone by angiotensin II primarily target G-protein signaling pathways. However, Walter Koch, Ph.D., the W.W. Smith Professor of Medicine and the Director of the Center for Translational Medicine and the George Zallie and Family Laboratory for Cardiovascular Gene Therapy, said that these data clearly show that beta-arrestin1 plays a more significant role in than G-proteins.

"Aldosterone secretion is dependent on beta-arrestin-1," Dr. Koch said. "It may not be independent of G-proteins, but beta-arrestin-1 is definitely the critical player. The goal should be to find a new antagonist that can block beta-arrestin-1 and G-protein activation equally well. Doing so would lead to lower aldosterone levels at its source and alleviate negative remodeling processes in the injured heart."

Source: Thomas Jefferson University

Explore further: Jefferson scientists use gene therapy to reverse heart failure in animals

Related Stories

Some antipsychotic drugs may be missing their mark

January 1, 2008

Drugs that treat depression, schizophrenia and other psychotic conditions and that target a particular protein on brain cells might not be triggering the most appropriate response in those cells, new research suggests.

Researchers Discover How Lithium Works

January 14, 2008

Despite more than 30 years of widespread use of lithium to control psychiatric disorders, such as bipolar disorder, scientists have been uncertain about how this drug actually works on a molecular level.

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.