In a finding that could open up a new realm of treatments for cardiovascular disease, UC Berkeley scientists say they've found that hardened arteries are actually caused by rogue stem cells in blood vessels that start multiplying after blood vessel walls are damaged, not by rogue muscle cells as previously suspected.

For the first time, we are showing evidence that vascular diseases are actually a kind of stem cell disease, UC Berkeley bioengineering professor Song Li, senior author of a paper documenting the discovery that appeared Wednesday in the journal Nature Communications, said in a statement Wednesday.

The researchers examined cells from mouse blood vessels and found that the ones that proliferated after vascular injury couldn't be traced back to smooth muscle cells, which are commonly thought to be the culprits behind clogged arteries (in combination with cholesterol and fat).

We did further tests and detected proteins and transcriptional factors that are only found in stem cells. No one knew that these cells existed in the blood vessel walls, because no one looked for them before, co-author Aijun Wang said in a statement.

The team is calling the newly identified stem cell type multipotent vascular stem cells. Their ability to differentiate into a variety of cell types, including bone and cartilage, could explain how blood vessels become hardened and brittle in the later stages of cardiovascular disease, according to Li.

In further experiments, the scientists confirmed that human blood vessels contain multipotent vascular stem cells after isolating them from arteries and coaxing them to develop into several different cell types.

Artery-blocking plaque forms as part of the body's natural immune response to blood vessel damage caused by low-density lipoprotein, also known as bad cholesterol. Researchers used to think that smooth muscle cells along the blood vessel walls helped form plaque by de-differentiating into a stem cell-like state, but Li and his team were suspicious because this process had never been directly documented in experiments.

Li said in an email that the next step is to establish a model for human blood vessel disease that can be used in the lab to screen drug candidates targeting the vascular stem cells.

The team has already applied for a grant from the California Institute for Regenerative Medicine to work on their blood vessel on a chip, Li says.

SOURCE: Tang et al. Differentiation of multipotent vascular stem cells contributes to vascular diseases. Nature Communications 2012 3: 875.

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