University at Buffalo (UB)
Thomas R. Cimato, MD, PhD, modeled how LDL cholesterol affects stem cell mobilization in humans by treating participants with statins of differing potencies.
Study Links Cholesterol with Atherosclerosis in Humans
Published October 7, 2013 This content is archived.
Story based on news release by Ellen Goldbaum
University at Buffalo translational researchers have confirmed in humans a link between LDL (“bad”) cholesterol levels and stem cells in the bloodstream that form atherosclerosis-causing inflammatory cells.
Because stem cells differentiate to form the cells that promote inflammation, controlling stem cell differentiation may play a key role in developing new treatments to supplement statins.
“Our research opens up a potential new approach to preventing heart attack and stroke by focusing on interactions between cholesterol and hematopoietic stem/progenitor cells (HSPCs),” says lead author Thomas R. Cimato, MD, PhD, assistant professor of medicine.
Cholesterol Increases Inflammation-Linked Molecule
The UB study confirmed findings in animals that high cholesterol recruits stem cells from the bone marrow into the bloodstream through increases in the cytokine interleukin-17 (IL-17).
This chemical signaling molecule has been implicated in chronic inflammatory diseases, including atherosclerosis. It boosts levels of granulocyte colony stimulating factor (G-CSF), which releases stem cells from the bone marrow.
Researchers at Columbia University previously revealed that disordered cholesterol metabolism increased circulating stem cell levels by increasing levels of both IL-17 and the HSPC-mobilizing cytokine G-CSF in the bloodstream.
LDL Cholesterol Modulates Cells That Lead to Plaque
The research team 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 researchers also found that statins reduce the levels of HSPCs in the blood, but not every patient responds similarly.
Jump from Mice to Humans ‘Remarkable’
“It’s quite remarkable that this connection between stem cells and LDL cholesterol in the blood holds true in humans,” says Cimato, whose lab is in the UB Clinical and Translational Science Institute.
Findings from animal studies don’t always translate to humans, Cimato notes.
Animal models have cholesterol levels two- to three-times higher than we generally encounter in patients who have a heart attack, he says. “This makes it unclear if the findings in the animals are relevant to the average patient.”
To make the jump from animals to humans, the year-long UB study — which involved a dozen people with no known coronary artery disease — required some creative steps.
“We modeled the mechanism of how LDL cholesterol affects stem cell mobilization in humans,” Cimato explains.
LDL cholesterol levels were manipulated with three different kinds of statins. Also, participants were on and off statin drugs for specified intervals (two weeks on, followed by one month off).
The next step will involve exploring the possible connection between HSPCs and cardiovascular events, such as heart attack and stroke, he says.
Research Published in PLOS One
The study, “LDL Cholesterol Modulates Human CD34+ HSPCs through Effects on Proliferation and the IL-17 G-CSF Axis,” has been published in PLOS One.
Other co-authors, all with the UB Department of Medicine, are Beth A. Palka, senior research support specialist; Jennifer K. Lang, MD, cardiology fellow; and Rebeccah F. Young, research scientist.
The research was funded by an American Heart Association Scientist Development Grant.