A new study led by Michigan Medicine has found that high levels of triglycerides — the most common type of fat found in our bodies and in the foods we eat — directly cause abdominal aortic aneurysms.
This challenges the long-held belief that triglycerides are simply biomarkers of vascular disease, showing instead that they actively contribute to aneurysm development, growth, and rupture.
The research, published in the American Heart Association journal Circulation, identified triglyceride-rich lipoproteins and proteins that regulate triglyceride metabolism, including APOC3 and ANGPTL3, as key drivers of abdominal aortic aneurysm.
Co-senior author Dr. Eugene Chen, Frederick G. L. Huetwell Professor of Cardiovascular Medicine at the University of Michigan Medical School, explained that while high lipid levels have long been recognized as a risk factor for aneurysms, this study pinpoints elevated triglycerides as a major contributor to their formation, growth, and risk of rupture.
The researchers used three different mouse models of hypertriglyceridemia and found a clear dose-dependent relationship: moderate triglyceride elevations sped up aneurysm formation, higher levels triggered aortic dissection, and extremely high levels led to severe complications consistent with aortic rupture.
Further analysis revealed how triglycerides cause damage. Elevated triglycerides and related fatty acids, especially palmitate, interfered with lysyl oxidase (LOX), an enzyme critical for maintaining the structural integrity of the aortic wall.
When LOX activity was impaired, the connective tissue weakened, accelerating aneurysm progression. By overexpressing LOX in the aorta, the team was able to block these harmful effects, confirming the mechanism.
Standard lipid-lowering drugs like niacin failed to lower triglycerides enough to offer protection. However, experimental antisense oligonucleotide therapy targeting ANGPTL3 — a liver-produced protein that affects fat breakdown — reduced triglyceride levels by up to 50% and successfully prevented aneurysm formation and dissection in the mouse models.
Co-senior author Dr. Yanhong Guo, research assistant professor of internal medicine at U-M Medical School, called the results an exciting step forward for a condition that currently has few treatment options beyond surgery.
She noted that the findings could shift how vascular diseases like abdominal aortic aneurysm are understood and treated, potentially giving high-risk patients a much-needed pharmacological option.
This study represents a significant advancement in vascular disease research by identifying triglycerides as not just a marker but a direct cause of abdominal aortic aneurysms. The demonstration of a specific mechanism involving lysyl oxidase, and the success of targeted ANGPTL3 therapy, opens the door to new treatments.
If future human trials confirm these findings, managing triglycerides could become a key strategy in preventing one of the most dangerous cardiovascular conditions.
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The study is published in Circulation.
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