The real culprit behind hardened arteries? Stem cells, says landmark study

ScienceDaily (June 6, 2012) 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 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.

The scar tissue, known as neointima, has certain characteristics of smooth muscle, the dominant type of tissue in the blood vessel wall. Because mature smooth muscle cells no longer multiply and grow, it was theorized that in the course of the inflammatory response, they revert, or de-differentiate, into an earlier state where they can proliferate and form matrices that contribute to plaque buildup.

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.

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The real culprit behind hardened arteries? Stem cells, says landmark study