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Prostaglandin receptor key to atherosclerosis development
Date:12/15/2008

Atherosclerosis a disease that includes the buildup of fatty, cholesterol-laden lumps of cells inside the artery wall is the underlying cause of heart attacks and strokes.

A team of Vanderbilt University Medical Center investigators has now demonstrated that a receptor for prostaglandin-E2 plays a key role in the development of atherosclerosis. The findings, reported this month in Cell Metabolism, point to this receptor and its signaling pathways as molecular targets for modulating atherosclerosis development.

Atherosclerosis is widely accepted to be an inflammatory disease process, involving immune system cells called macrophages.

"The first visible lesion in atherosclerosis looking under a microscope is the accumulation of cholesterol in macrophages or foam cells," said MacRae Linton, M.D., professor of Medicine and Pharmacology and senior author of the current studies. Since a major product of activated macrophages is prostaglandin-E2 (an inflammation-related signaling molecule), Linton and colleagues reasoned that this compound may play an important role in atherosclerosis.

Mounting evidence supports roles for prostaglandins and their receptors in atherosclerosis, but only two prostacyclin and thromboxane-A2 have been considered in detail, he said.

Linton, first author Vladimir Babaev, M.D., Ph.D., co-senior author Sergio Fazio, M.D., Ph.D., and colleagues focused on two receptors for prostaglandin-E2, called EP2 and EP4, because they were known to be expressed by cells in human atherosclerotic plaques.

To study the roles of these receptors in atherosclerosis, the investigators performed a modified bone marrow transplant to develop mice in which the blood cells lacked either the EP2 or the EP4 receptor. They transplanted the blood-forming cells into mice missing the LDL receptor a widely used model for studies of atherosclerosis because these mice rapidly develop plaques when fed a high-fat diet.
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Contact: Kathy Whitney
kathy.f.whitney@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert

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