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U-M researchers find new way to clear cholesterol from the blood
Date:4/10/2013

ANN ARBORResearchers at the University of Michigan have identified a new potential therapeutic target for lowering cholesterol that could be an alternative or complementary therapy to statins.

Scientists in the lab of David Ginsburg at the Life Sciences Institute inhibited the action of a gene responsible for transporting a protein that interferes with the ability of the liver to remove cholesterol from the blood in mice. Trapping the destructive protein where it couldn't harm receptors responsible for removing cholesterol preserved the liver cells' capacity to clear plasma cholesterol from the blood, but did not appear to otherwise affect the health of the mice.

In the research, published April 9 in the online journal eLife, scientists found that mice with an inactive SEC24A gene could develop normally. However, their plasma cholesterol levels were reduced by 45 percent because vesicles from liver cells were not able to recruit and transport a critical regulator of blood cholesterol levels called proprotein convertase subtilisin/kexin type 9. PCSK9 is a secretory protein that destroys the liver cells' receptors of low-density lipoprotein LDL, the so-called "bad cholesterol"and prevents the cells from removing the LDL.

"Inhibiting SEC24A or PCSK9 may be an alternative to statins, and could work together with statins to produce even greater effects," said Xiao-Wei Chen of the Ginsburg lab, the first author on the paper. "Also, they might be effective on patients who are resistant to or intolerant of statins."

Initial studies of anti-PCSK9 therapies in humans have shown that eliminating PCSK9 can lower cholesterol dramatically and work with statins like Lipitor to lower it even further. The Ginsburg lab's research points to a new area for study: rather than inhibiting PCSK9 itself, perhaps future therapies could block the transport mechanism that allows the destructive protein to reach the LDL receptors.

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Contact: Laura J. Williams
laurajw@umich.edu
734-615-4862
University of Michigan
Source:Eurekalert

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