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To predict atherosclerosis, follow the disturbed blood flow
Date:6/23/2010

e and effect, Jo says.

"We have developed a model where we disturb blood flow in the carotid artery by partial ligation, and atherosclerosis appears within two weeks," he says. "This rapid progression allows us to demonstrate cause and effect, and to examine the landmark events at the beginning of the process."

Jo says that endothelial cells, which form the inner lining of blood vessels, are equipped with sensors that detect changes in fluid flow.

"Disturbed flow is what causes the endothelial cells to become inflamed," he says.

The inflammation resulting from "bad flow" conditions in a stretch of artery causes white blood cells to accumulate there, followed by buildup of cholesterol and lipids and plaque formation.

Just 48 hours after blood flow in the carotid arteries was disturbed, Ni and colleagues dissected the carotid arteries from the mice and used genome-wide microarray technology to identify hundreds of genes that were turned on or off in the endothelial cells.

In past experiments, scientists grew endothelial cells in dishes to probe how different patterns of fluid flow affected their patterns of genes. However, growing cells in dishes alters them enough that many of the genes Jo's team found have not been identified before in this context.

For example, the team showed that the gene LMO4 not previously known to be involved in atherosclerosis -- is turned on in their mouse model and also in human coronary arteries. Scientists studying breast cancer think LMO4 is involved in tumor migration and invasion, making an interesting parallel between atherosclerosis and cancer, Jo says.

He says his laboratory is now probing which of the newly identified genes are most important in atherosclerosis and searching for ways to manipulate them with drugs or genetic techniques, with an eye towards possible diagnostic and pharmaceutical applications.


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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University
Source:Eurekalert  

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