Preventing or reversing inflammation after heart attack, stroke may require 2-pronged approach

Mar 01, 2010

Researchers at Albany Medical College are releasing results of a study this week that they say will help refocus the search for new drug targets aimed at preventing or reversing the devastating tissue inflammation that results after heart attack and stroke.

In the March 5 issue of the , lead author Alejandro P. Adam and his colleagues at the college's Center for Cardiovascular Science are reporting that vascular cells' ability to properly regulate fluid movement is not necessarily affected solely by the activity of an enzyme that for years has been in the crosshairs of scientists and pharmaceutical developers.

"Learning the mechanisms of inflammation is a key step in the development of new and better therapies to improve the outcome of widespread pathologies, such as stroke, heart attack, and ," said Adam, a postdoctoral fellow at the cardiovascular center. "To determine which are the best targets for treatment, we need to understand exactly what role each molecule is playing in the regulation of the vessel walls, and we found that the enzyme Src may be needed to get changes in barrier function but by itself is not sufficient."

Blood vessels, which form a tight barrier between blood and the surrounding tissues, are composed of endothelial cells that act as gatekeepers, controlling how, when and where molecules of water, solutes and pass through them into the body's tissues.

Previous studies have shown blocking the enzyme Src altered the structure of a protein known to hold the endothelial cells together, thus, keeping their barriers tight and limiting caused by fluid accumulation, or edema.

"We found that Src indeed adds several phosphates to this protein, but this addition of the did not alter barrier function of the endothelial cells," explained professor Peter A. Vincent, who oversaw the team's research. "These findings suggest other pathways are needed for Src to change permeability and open the door to future studies to determine what these other signals are."

There are many "adhesion molecules" involved in holding endothelial cells together and many signaling molecules that tell the adhesion molecules when to hold onto or release each other. Vincent's team is moving forward with what he calls a "two-hit model" - the idea that endothelial cells require two different signals to open up cell-cell connections and allow the passage of fluids.

"Many factors lead to a complex array of signals inside the endothelial cells to promote this loss of barrier function," Adam said. "A two-hit model would explain much better than a single-hit model the regulation of the vascular permeability. On the pharmacological side, it would allow us to propose other drug targets to prevent or reverse inflammation and edema."

By being named a "Paper of the Week" by the Journal of Biological Chemistry, the article by Adam and Vincent, graduate student Amy L. Sharenko and associate professor Kevin Pumiglia has been categorized in the top 1 percent of papers reviewed by the journal's editorial board in terms of significance and overall importance.

Explore further: Breakthrough points to new drugs from nature

Provided by American Society for Biochemistry and Molecular Biology

not rated yet
add to favorites email to friend print save as pdf

Related Stories

Deciphering the body's healing secrets

Feb 12, 2009

Healthy blood vessels play a key role in the prevention and treatment of diseases such as cardiovascular disease and diabetes. Endothelial cells line the blood vessels and are critical to the regulation of blood vessel growth ...

Building the blood-brain barrier

Oct 27, 2008

Construction of the brain's border fence is supervised by Wnt/b-catenin signaling, report Liebner et al. in The Journal of Cell Biology.

Bone marrow cells can heal nerves in diabetes model

Feb 04, 2009

Transplanting cells that replenish blood vessels can also restore nerve function in an animal model of diabetic neuropathy, Emory researchers have found. The results are described online this week in the journal Circulation.

Recommended for you

Breakthrough points to new drugs from nature

5 hours ago

Researchers at Griffith University's Eskitis Institute have developed a new technique for discovering natural compounds which could form the basis of novel therapeutic drugs.

World's first successful visualisation of key coenzyme

6 hours ago

Japanese researchers have successfully developed the world's first imaging method for visualising the behaviour of nicotine-adenine dinucleotide derivative (NAD(P)H), a key coenzyme, inside cells. This feat ...

User comments : 0

More news stories

Breakthrough points to new drugs from nature

Researchers at Griffith University's Eskitis Institute have developed a new technique for discovering natural compounds which could form the basis of novel therapeutic drugs.

A greener source of polyester—cork trees

On the scale of earth-friendly materials, you'd be hard pressed to find two that are farther apart than polyester (not at all) and cork (very). In an unexpected twist, however, scientists are figuring out ...

How kids' brain structures grow as memory develops

Our ability to store memories improves during childhood, associated with structural changes in the hippocampus and its connections with prefrontal and parietal cortices. New research from UC Davis is exploring ...

Gate for bacterial toxins found

Prof. Dr. Dr. Klaus Aktories and Dr. Panagiotis Papatheodorou from the Institute of Experimental and Clinical Pharmacology and Toxicology of the University of Freiburg have discovered the receptor responsible ...