Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
>
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

How ‘Bad’ Cholesterol Causes Atherosclerosis in Humans: Stem cells play a Key Role

Published: Monday, September 30, 2013
Last Updated: Monday, September 30, 2013
Bookmark and Share
Study translates to humans a finding previously shown in lab animals that could lead to new therapy to use with statins or in place of them.

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.

Co-authors with Cimato are Beth A. Palka, senior research support specialist, Jennifer K. Lang, MD, cardiology fellow and Rebeccah F. Young, research scientist, all of the Department of Medicine and UB’s CTRC.

The research was funded by an American Heart Association Scientist Development Grant.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Engineered Blood Vessels Function like Native Tissue
Researchers says that blood vessels that have been tissue-engineered from bone marrow adult stem cells may serve as a patient's own source of new blood vessels.
Wednesday, July 11, 2007
Scientific News
A Gene-Sequence Swap Using CRISPR to Cure Haemophilia
For the first time chromosomal defects responsible for hemophilia have been corrected in patient-specific iPSCs using CRISPR-Cas9 nucleases
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
New Weapon in the Fight Against Blood Cancer
This strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Zebrafish Reveal Drugs that may Improve Bone Marrow Transplant
Compounds boost stem cell engraftment; could allow more matches for patients with cancer and blood diseases.
New Material Forges the Way for 'Stem Cell Factories'
Researchers have discovered the first fully synthetic substrate with potential to grow billions of stem cells. The researchcould forge the way for the creation of 'stem cell factories' - the mass production of human embryonic (pluripotent) stem cells.
Liver Regrown from Stem Cells
Scientists have repaired a damaged liver in a mouse by transplanting stem cells grown in the laboratory.
Immunotherapy Shows Promise for Myeloma
A strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
'Google Maps' for the Body
Scientists have revealed research that uses previously top-secret technology to zoom through the human body down to the level of a single cell that could be a game-changer for medicine.
Adaptimmune's Novel Cancer Therapeutics Show Positive Clinical Trial Results
The company has announced that positive data from its Phase I/II study of its affinity enhanced T-cell receptor (TCR) therapeutic targeting the NY-ESO-1 cancer antigen in patients with multiple myeloma has been published.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!