Featured Research

from universities, journals, and other organizations

New way to clear cholesterol from the blood

Date:
April 10, 2013
Source:
University of Michigan
Summary:
Researchers have identified a new potential therapeutic target for lowering cholesterol that could be an alternative or complementary therapy to statins.

Researchers 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.

Related Articles


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.

The paper, "SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion," explains the mechanism by which cells transport PCSK9. Vesicles transport proteins in the cell; the Ginsburg lab's research focused on a specialized type of vesicle packaged by the Coat Protein Complex II, which regulates the metabolism of cholesterol, among many other things. 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," Chen said.

The part of the vesicle that selects which proteins to transport is SEC24. By blocking SEC24A gene, the researchers disabled the vesicle's selection of PCSK9. The destructive protein remained trapped within the cells, leaving the LDLR intact and enabling the liver to clear the body of cholesterol that otherwise could accumulate in arteries.

"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.

Ginsburg is a research professor at the Life Sciences Institute, where his laboratory is located. He is also the James V. Neel Distinguished University Professor and the Warner-Lambert/Parke-Davis Professor in the Division of Molecular Medicine and Genetics, Department of Internal Medicine and departments of Human Genetics and Pediatrics at the U-M Medical School and a Howard Hughes Medical Institute Investigator.


Story Source:

The above story is based on materials provided by University of Michigan. Note: Materials may be edited for content and length.


Journal Reference:

  1. X.-W. Chen, H. Wang, K. Bajaj, P. Zhang, Z.-X. Meng, D. Ma, Y. Bai, H.-H. Liu, E. Adams, A. Baines, G. Yu, M. A. Sartor, B. Zhang, Z. Yi, J. Lin, S. G. Young, R. Schekman, D. Ginsburg. SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion. eLife, 2013; 2 (0): e00444 DOI: 10.7554/eLife.00444

Cite This Page:

University of Michigan. "New way to clear cholesterol from the blood." ScienceDaily. ScienceDaily, 10 April 2013. <www.sciencedaily.com/releases/2013/04/130410141535.htm>.
University of Michigan. (2013, April 10). New way to clear cholesterol from the blood. ScienceDaily. Retrieved March 29, 2015 from www.sciencedaily.com/releases/2013/04/130410141535.htm
University of Michigan. "New way to clear cholesterol from the blood." ScienceDaily. www.sciencedaily.com/releases/2013/04/130410141535.htm (accessed March 29, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, March 29, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

S. Leone in New Anti-Ebola Lockdown

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015) — Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17 Video provided by AFP
Powered by NewsLook.com
These Popular Antibiotics Can Cause Permanent Nerve Damage

These Popular Antibiotics Can Cause Permanent Nerve Damage

Newsy (Mar. 27, 2015) — A popular class of antibiotic can leave patients in severe pain and even result in permanent nerve damage. Video provided by Newsy
Powered by NewsLook.com
WH Plan to Fight Antibiotic-Resistant Germs

WH Plan to Fight Antibiotic-Resistant Germs

AP (Mar. 27, 2015) — The White House on Friday announced a five-year plan to fight the threat posed by antibiotic-resistant bacteria amid fears that once-treatable germs could become deadly. (March 27) Video provided by AP
Powered by NewsLook.com
House Ready to Pass Medicare Doc Bill

House Ready to Pass Medicare Doc Bill

AP (Mar. 26, 2015) — In rare bipartisan harmony, congressional leaders pushed a $214 billion bill permanently blocking physician Medicare cuts toward House passage Thursday, moving lawmakers closer to resolving a problem that has plagued them for years. (March 26) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins