BERKELEY One of the top suspects behind killer vascular diseases is the victim of mistaken identity, according to researchers from the University of California, Berkeley, who used genetic tracing to help hunt down the real culprit. The guilty party is not the smooth muscle cells within blood vessel walls, which for decades was thought to combine with cholesterol and fat that can clog arteries. Blocked vessels can eventually lead to heart attacks and strokes, which account for one in three deaths in the United States.
Instead, a previously unknown type of stem cell a multipotent vascular stem cell is to blame, and it should now be the focus in the search for new treatments, the scientists report in a new study appearing today (June 6) in the journal Nature Communications.
"For the first time, we are showing evidence that vascular diseases are actually a kind of stem cell disease," said principal investigator Song Li, professor of bioengineering and a researcher at the Berkeley Stem Cell Center. "This work should revolutionize therapies for vascular diseases because we now know that stem cells rather than smooth muscle cells are the correct therapeutic target."
The finding that a stem cell population contributes to artery-hardening diseases, such as atherosclerosis, provides a promising new direction for future research, the study authors said.
"This is groundbreaking and provocative work, as it challenges existing dogma," said Dr. Deepak Srivastava, who directs cardiovascular and stem cell research at the Gladstone Institutes in San Francisco, and who provided some of the mouse vascular tissues used by the researchers. "Targeting the vascular stem cells rather than the existing smooth muscle in the vessel wall might be much more effective in treating vascular disease."
It is generally accepted that the buildup of artery-blocking plaque stems from the body's immune response to vessel damage caused by low-density lipoproteins, the bad cholesterol many people try to eliminate from their diets. Such damage attracts legions of white blood cells and can spur the formation of fibrous scar tissue that accumulates within the vessel, narrowing the blood flow.
However, no experiments published have directly demonstrated this de-differentiation process, so Li and his research team remained skeptical. They turned to transgenic mice with a gene that caused their mature smooth muscle cells to glow green under a microscope.
In analyzing the cells from cross sections of the blood vessels, they found that more than 90 percent of the cells in the blood vessels were mature smooth muscle cells. They then isolated and cultured the cells taken from the middle layer of the mouse blood vessels.
After one month of cell expansion, the researchers saw a threefold increase in the size of the cell nucleus and the spreading area, along with an increase in stress fibers. Notably, none of the new, proliferating cells glowed green, which meant that their lineage could not be traced back to the mature smooth muscle cells originally isolated from the blood vessels.
"Not only was there a lack of green markers in the cell cultures, but we noticed that another type of cell isolated from the blood vessels exhibited progenitor traits for different types of tissue, not just smooth muscle cells," said Zhenyu Tang, co-lead author of the study and a Ph.D. student in the UC Berkeley-UCSF Graduate Program in Bioengineering.
Originally posted here:
Stem cells real culprit behind hardened arteries
