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New technique found to remove cholesterol from blood

By Catholic Online (NEWS CONSORTIUM)
April 15th, 2013
Catholic Online (www.catholic.org)

Trapping the destructive protein where it couldn't harm receptors responsible for removing cholesterol is a goal by many researchers. While statins have proved successful in the maintenance of "bad cholesterol," many patients have received no demonstrable benefit from their use. Scientists, led by Professor David Ginsburg of the University of Michigan's Howard Hughes Medical Institute have now 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.

LOS ANGELES, CA (Catholic Online) - Scientists found that mice with an inactive SEC24A gene could develop normally. The mice's plasma cholesterol levels were reduced by 45 percent due to 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).

PCSK9, a secretory protein that destroys the liver cells' receptors of low-density lipoprotein, or 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," Dr. Xiao-Wei Chen from the Howard Hughes Medical Institute says. "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 as well as work with statins like Lipitor to lower it even further. The new study 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.

Professor Ginsburg's team focused on a specialized type of vesicle packaged by the Coat Protein Complex II, which regulates the metabolism of cholesterol. These vesicles selectively transport cargo proteins including PCSK9.

Without those LDL receptors (LDLR), liver cells are not able to remove LDLs from the bloodstream, so protecting the LDLR from PCSK9 would allow the receptors to continue to remove cholesterol.

"Without SEC24A, much of the PCSK9 couldn't make its way out of the cells to destroy the LDLR, which then clears cholesterol from the blood," a researcher said.

 "We have no reason at this point to expect that this strategy will be any better than anti-PCSK9 therapy for treating high cholesterol, but it would be another alternative approach, and it's hard to predict which drugs will work the best and be the safest until we actually try them out in people," Ginsburg said.

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