Featured Research

from universities, journals, and other organizations

How 'bad' cholesterol causes atherosclerosis in humans: Stem cells play a key role

Date:
September 23, 2013
Source:
University at Buffalo
Summary:
Translational researchers are developing a richer understanding of atherosclerosis in humans, revealing a key role for stem cells that promote inflammation.

University at Buffalo translational researchers are developing a richer understanding of atherosclerosis in humans, revealing a key role for stem cells that promote inflammation.

The research was published last month in PLOS One. It extends to humans previous findings in lab animals by researchers at Columbia University that revealed that high levels of LDL ("bad") cholesterol promote atherosclerosis by stimulating production of hematopoietic stem/progenitor cells (HSPC's).

"Our research opens up a potential new approach to preventing heart attack and stroke, by focusing on interactions between cholesterol and the HSPCs," says Thomas R. Cimato, MD, PhD, lead author on the PLOS One paper and assistant professor in the Department of Medicine in the UB School of Medicine and Biomedical Sciences.

He notes that the finding about the importance of these stem cells in atherosclerosis could lead to the development of a useful therapy in combination with statins, or one that could be used in place of statins in individuals who cannot tolerate them.

The study demonstrated for the first time in humans that high total cholesterol recruits stem cells from the bone marrow into the bloodstream, via increases in IL-17, which has been implicated in many chronic inflammatory diseases, including atherosclerosis. IL-17 boosts levels of granulocyte colony stimulating factor (GCSF), which releases stem cells from the bone marrow.

They also found that statins do reduce the levels of HSPCs in the blood but not every subject responded similarly, Cimato says.

"We've extrapolated to humans what other scientists previously found in mice about the interactions between LDL cholesterol and these HSPCs," explains Cimato.

The demonstration that a finding in lab animals is equally relevant in humans is noteworthy, adds Cimato, a researcher in UB's Clinical and Translational Research Center (CTRC).

"This is especially true with cholesterol studies," he says, "because mice used for atherosclerosis studies have very low total cholesterol levels at baseline. We feed them very high fat diets in order to study high cholesterol but it isn't easy to interpret what the levels in mice will mean in humans and you don't know if extrapolating to humans will be valid."

Cimato adds that the degree of increased LDL cholesterol in mouse studies is much higher than what is found in patients who come to the hospital with a heart attack or stroke.

"The fact that this connection between stem cells and LDL cholesterol in the blood that was found in mice also turns out to be true in humans is quite remarkable," he says.

Cimato explains that making the jump from rodents with very high LDL cholesterol to humans required some creative steps, such as the manipulation of the LDL cholesterol levels of subjects through the use of three different kinds of statins.

The study involved monitoring for about a year a dozen people without known coronary artery disease who were on the statins for two-week periods separated by one-month intervals when they were off the drugs.

"We modeled the mechanism of how LDL cholesterol affects stem cell mobilization in humans," says Cimato.

The UB researchers found that LDL cholesterol modulates the levels of stem cells that form neutrophils, monocytes and macrophages, the primary cell types involved in the formation of plaque and atherosclerosis.

The next step, he says, is to find out if HSPCs, like LDL cholesterol levels, are connected to cardiovascular events, such as heart attack and stroke.


Story Source:

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


Journal Reference:

  1. Thomas R. Cimato, Beth A. Palka, Jennifer K. Lang, Rebeccah F. Young. LDL Cholesterol Modulates Human CD34 HSPCs through Effects on Proliferation and the IL-17 G-CSF Axis. PLoS ONE, 2013; 8 (8): e73861 DOI: 10.1371/journal.pone.0073861

Cite This Page:

University at Buffalo. "How 'bad' cholesterol causes atherosclerosis in humans: Stem cells play a key role." ScienceDaily. ScienceDaily, 23 September 2013. <www.sciencedaily.com/releases/2013/09/130923114154.htm>.
University at Buffalo. (2013, September 23). How 'bad' cholesterol causes atherosclerosis in humans: Stem cells play a key role. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2013/09/130923114154.htm
University at Buffalo. "How 'bad' cholesterol causes atherosclerosis in humans: Stem cells play a key role." ScienceDaily. www.sciencedaily.com/releases/2013/09/130923114154.htm (accessed August 28, 2014).

Share This




More Health & Medicine News

Thursday, August 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Mini Pacemaker Has No Wires

Mini Pacemaker Has No Wires

Ivanhoe (Aug. 27, 2014) Cardiac experts are testing a new experimental device designed to eliminate major surgery and still keep the heart on track. Video provided by Ivanhoe
Powered by NewsLook.com
After Cancer: Rebuilding Breasts With Fat

After Cancer: Rebuilding Breasts With Fat

Ivanhoe (Aug. 27, 2014) More than 269 million women are diagnosed with breast cancer each year. Many of them will need surgery and radiation, but there’s a new simple way to reconstruct tissue using a patient’s own fat. Video provided by Ivanhoe
Powered by NewsLook.com
Blood Clots in Kids

Blood Clots in Kids

Ivanhoe (Aug. 27, 2014) Every year, up to 200,000 Americans die from a blood clot that travels to their lungs. You’ve heard about clots in adults, but new research shows kids can get them too. Video provided by Ivanhoe
Powered by NewsLook.com
Radio Waves Knock out Knee Pain

Radio Waves Knock out Knee Pain

Ivanhoe (Aug. 27, 2014) Doctors have used radio frequency ablation or RFA to reduce neck and back pain for years. But now, that same technique is providing longer-term relief for patients with severe knee pain. Video provided by Ivanhoe
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:
from the past week

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