Changing your identity to protect others might sound like something reserved for comic book vigilantes, but a study led by researchers at the Stanford University School of Medicine has found a select group of cells in artery walls do just that. For these cells, the identity shift happens in a disease called atherosclerosis, which occurs when arteries get clogged by plaque, a buildup of fats, cholesterol and molecular particulate.
Exercise to atherosclerosis
“Researcher know that things like poor diet and lack of exercise contribute to atherosclerosis,” said Thomas Quertermous, MD, professor of cardiovascular medicine at Stanford. “But molecularly speaking, researchers still don’t know how the disease progresses or, conversely, is hindered.” This new work, he said, takes a big step toward addressing that question.
Plaque grows within the layers of tissue that form the artery; so as oppose to inside the tube itself; so causing the blood conduit to narrow. Too much plaque tears open the tissue; hence allowing the built-up gunk to flood the interior of the tube. That leads to a clot, which can cause artery blockage and often a heart attack. In people with atherosclerosis, cells that make up the artery wall transform; also invade the area containing the plaque, or lesion, and form something called a fibrous cap; which acts kind of like a lid to prevent the plaque from bursting into the artery.
The team has also pinpoint a gene that seems to be behind the cells’ transformation. What’s more, when they look at populationwide genomic data; so they saw that individuals; who had more activity in this particular gene were at a decrease risk for heart attack. “Logically, it makes sense the more cells that help form the fibrous cap; so the stronger the protection against plaque rupture; also therefore the less risk of a heart attack,” said Quertermous, who is the William G. Irwin Professor in Cardiovascular Medicine.
Collection of cells immune
Wirka and Quertermous then profile all the cells in the artery; so analyze the collection of cells immune, smooth muscle, fibromyocyte and more and ran gene expression analyses to see which genes were “on” in each individual cell. According to the gene expression analysis, the red-label smooth muscle cells that migrate to the plaque were sporting a new look.
“These cells exhibit a sort of swap: Patterns of gene activity that track with smooth muscle cells decreased; also activity of genes that give rise to fibromyocytes increase,” Quertermous said. “The data allow us to, beyond a shadow of a doubt; so characterize these particular cells in the plaque as smooth muscle cells that have turn into fibromyocytes.” Remarkably, Wirka said, the researchers find no evidence that smooth muscle cells transform into plaque-destabilizing immune cells; so resolving a long-standing question in the field.
Quertermous and Wirka said that TCF21 could likely help guide them; hence toward a new therapy for coronary artery disease. But before taking steps in that direction, there’s still more to understand about TCF21 and how it mediates this transformation at the molecular level; so they said. “Now we have good evidence that the ability for smooth muscle cells to undergo this transformation to fibromyocytes is important to protect against clinically significant coronary disease, but the timing and extent of this transformation is likely also important,” Wirka said.