Preventing heart attacks and strokes: LMP scientists reveal the role of type VIII collagen in preventing plaque rupture

Wednesday, October 16, 2013
Josh Lopes and Professor Michelle Bendeck
Josh Lopes and Professor Michelle Bendeck

In Canada, every seven minutes someone dies from a heart attack or stroke. But what if the incidence of this leading cause of death could be reduced? Researchers at the Department of Laboratory Medicine and Pathobiology (LMP) have revealed that an extracellular matrix protein, called type VIII collagen, provides stability to arterial atherosclerotic plaques and reduces the likelihood that they will rupture and cause a heart attack or stroke.

Professor Michelle Bendeck (PhD), along with fourth-year PhD candidate Josh Lopes, has been investigating how type VIII collagen could potentially prevent these deadly occurrences. Their recently published research in the American Journal of Pathology focuses on how type VIII collagen stabilizes part of the atherosclerotic plaque called the fibrous cap.

“Our research shows that type VIII collagen is deposited by cells in the fibrous cap on top of the plaque and has an important function in maintaining the strength of the cap. This prevents the erosion of a plaque which could trigger a heart attack or stroke,” said Prof. Bendeck.

Their findings are particularly intriguing because scientists previously believed that type VIII collagen should be completely suppressed, since it acts like the key in the ignition of cells when an artery is inflamed. It allows smooth muscle cells to easily multiply, migrate and invade from the outer vessel wall towards the inner vessel lumen. This causes plaques to form and can lead to a blocked artery.

While their research supported the view that type VIII collagen can cause plaques to form, Prof. Bendeck and Lopes also identified a more positive role. Lopes explained, “Scientists previously thought that this molecule should be suppressed entirely because it causes plaque growth and atherosclerosis. But we show that type VIII collagen has a duality – it can be beneficial at some points in the development of the disease and harmful at others.”

Using mouse models, they discovered that apolipoprotein E, an essential component of high-density lipoprotein (HDL), suppresses the expression of type VIII collagen. “If we can regulate the production of type VIII collagen with apolipoprotein E in late atherosclerosis, we can potentially prevent plaques from rupturing,” Lopes added.

What are the future clinical implications? While doctors currently use ultrasound to locate plaques in their patients, it is difficult for them to identify whether the plaques are unstable. Lopes explained, “Once technology advances, and we’re able to identify plaques that are particularly unstable, we can potentially give patients a medication to stimulate the production of type VIII collagen. It won’t cause the lesion to shrink, but it can certainly make the lesion a bit more stable.”

Prof. Bendeck and Lopes are working with other labs to determine the biological processes and features that they can measure in plaques. “We’re planning to image plaques in mice using ultrasound, and measure these biological processes within mice that are deficient in type VIII collagen,” said Lopes. “We’re also investigating how this protein interacts with other proteins. You’re talking about the forefront of medicine – what we can and can’t do – so it’s pretty exciting.”