The US Brain Aneurysm Foundation (BAF) has highlighted a new study from the University of California San Francisco (UCSF; San Francisco, USA) that offers an explanation as to how brain aneurysms form and weaken, and could point toward new ways of identifying which cases are most dangerous. The findings—published this week in Nature Neuroscience—reveal a destructive feedback loop between scar-forming cells and immune cells within human artery walls that gradually weakens the vessel.
This work, which was supported by BAF funding in its early stages and led by senior author Ethan Winkler (UCSF, San Francisco, USA), could lead to new ways of predicting which aneurysms are most likely to rupture—and, eventually, to treatments that stabilise them before they rupture as well.
“Clinicians traditionally have relied on the size and location of an aneurysm to estimate its danger. By revealing the biology that drives an aneurysm to weaken, Dr Winkler and his team have opened a path toward predicting risk far more accurately,” said Christine Buckley, executive director of the BAF. “This is an important step forward for the field and for the millions of people living with an aneurysm, and it may transform our understanding of who is most at risk of rupture. This is exactly the kind of discovery we hope to make possible when we fund bold ideas.”
Analysing more than 100,000 individual cells from human aneurysms and healthy brain arteries, the UCSF team identified 19 distinct cell types and mapped how they are organised within the vessel wall. In aneurysm tissue, supportive smooth muscle cells had disappeared and been replaced by stiff, scar-forming cells called fibroblasts. A type of immune cell called a macrophage accumulated nearby, and the two cell types reinforced one another in a damaging cycle: the fibroblasts released a signal that prompted the macrophages to produce enzymes that break down the vessel’s structural support, further weakening the wall. When researchers blocked that signal, the macrophages produced fewer destructive enzymes.
While brain aneurysms can be repaired through surgery or minimally invasive procedures, their size is an unreliable predictor of risk, and smaller aneurysms are typically monitored rather than being treated. By pointing to the biological processes that weaken vessel walls, this new research could help physicians identify dangerous aneurysms earlier and intervene sooner rather than waiting for size thresholds that may not capture the true risk.
“Foundational discoveries like this one don’t happen without early support,” Winkler averred. “We are grateful to the BAF for their willingness to invest in understanding the basic biology of how aneurysms form, as that early funding gave us the opportunity to advance this work. Continuing to fund early-stage research is how our field will keep moving toward better answers, and better outcomes, for patients.”
