New research from the University of California, San Francisco shows how certain cells in the brain weaken and rupture aneurysms. This helps explain why some aneurysms rupture and others don’t, and could lead to new ways to predict and prevent strokes.
A brain aneurysm is a bulge in a blood vessel that may go unnoticed for years. If it ruptures, it can cause a severe and often fatal type of stroke. About 1 in 50 Americans suffers from a brain aneurysm, but doctors still struggle to predict which ones are most dangerous.
A new study helps unravel the biology behind these events by mapping the cells in artery walls and the interactions that weaken them.
“We have taken a major step toward solving the mystery of how aneurysms form,” said Ethan Winkler, MD, assistant professor of neurosurgery and senior author of the study. natural neuroscience. “We identified the characters involved and saw which characters were involved in different stages of the disease.”
Although aneurysms can be repaired with surgery or other minimally invasive procedures, treatment decisions are primarily based on aneurysm size, location, and patient-specific risk factors. Aneurysms smaller than 7 millimeters are usually monitored rather than repaired, although there is no reliable way to predict which aneurysms will rupture.
Cells usually have three layers, but…
The researchers analyzed more than 100,000 individual cells taken from human aneurysms and healthy brain arteries, identifying 19 different cell types and determining which genes were active in each. They also mapped how cells are organized within blood vessel walls.
Healthy arteries are made up of three layers. A thin inner layer, a thick smooth muscle layer in the middle that allows the artery to expand and contract with each heartbeat, and an outer layer of fibroblasts that provide structure.
In aneurysm tissue, these rings were disorganized and many of the smooth muscle cells had disappeared. Instead, there were scar-forming fibroblasts, which the researchers called “activated fibroblasts,” which stiffened the arterial walls and made them less likely to bend as blood pulsated. These cells expressed genes associated with genetic risk for aneurysms.
The researchers focused on a specific type of macrophage (immune cell) that accumulates near fibroblasts within the artery wall. Surprisingly, the researchers discovered that these macrophages expressed genes normally associated with bone tissue.
Further experiments revealed the existence of a destructive feedback loop between these two cell types. Activated fibroblasts released signals that caused these macrophages to produce enzymes that degrade the structural supports of blood vessels. When scientists blocked that signal, macrophages were less likely to produce these enzymes.
Explaining the small aneurysm paradox
This study describes the process by which blood vessel walls gradually weaken. First, supporting muscle cells are lost, then hard scar tissue accumulates and inflammatory immune cells are activated.
This finding helps explain the clinical paradox that small aneurysms, often considered low-risk, can rupture. Winkler noted that more than half of the ruptures he treated early in his career occurred in aneurysms smaller than 7 millimeters, the typical surgical threshold.
Without understanding the underlying biology, we had to rely on anatomy. ”
Ethan Winkler, MD, assistant professor of neurosurgery and senior author of the study
A better understanding of how aneurysms form creates opportunities to intervene early, either by blocking the signals sent by fibroblasts or by inhibiting the immune response to those signals.
“Maybe one day we will be able to stabilize an aneurysm and prevent it from rupturing,” Winkler said. “It’s a very effective treatment and something we’ve been dreaming of for a long time.”
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University of California, San Francisco
