MADRID, 17 (EUROPA PRESS)
Researchers at the University of Michigan (UM) have discovered in a study using mouse models that high levels of triglycerides, the most common type of fat in the body and in food, directly cause abdominal aortic aneurysms.
The results, published in Circulation, challenge the traditional belief that triglycerides are simply biomarkers of vascular disease, demonstrating that they actually play a direct, pathogenic role in the development, growth, and rupture of aneurysms.
Specifically, the team identified triglyceride-rich lipoproteins and proteins that regulate triglyceride metabolism, including APOC3 and ANGPTL3, as causal drivers of abdominal aortic aneurysm in mice.
"We've known that hyperlipidemia is a risk factor for aortic aneurysms, but this multidimensional study points to hypertriglyceridemia (high triglyceride levels) as a key contributor to the development and growth, as well as dissection and rupture, of aortic aneurysms," explained co-senior author Eugene Chen, a professor at the University of Michigan Medical School.
During the study, the scientists used three different mouse models of hypertriglyceridemia, confirming that aneurysm severity depended on triglyceride levels. Moderate increases in this fat accelerated aneurysm formation, while higher levels led to aortic dissection.
Similarly, mice with severely elevated triglyceride concentrations developed more severe complications consistent with aortic rupture.
THERAPEUTIC STRATEGY
Based on these results, the researchers speculated that controlling triglycerides could become a powerful therapeutic strategy.
After trying several treatments, they were successful with an experimental antisense oligonucleotide therapy. The drug candidate targets the ANGPTL3 protein, secreted in the liver and affecting the breakdown of fats in the body.
The treatment dramatically reduced triglyceride levels by up to 50 percent and prevented aneurysm formation and dissection in multiple mouse models.
"This therapy has great potential as a treatment for abdominal aortic aneurysm, and our research lays the groundwork for future clinical trials," said co-senior author Yanhong Guo, a research assistant professor of internal medicine at the UM Medical School and a member of the UM Health Frankel Cardiovascular Center.
In conclusion, the authors welcomed this key advance, which could represent a paradigm shift for vascular diseases such as abdominal aortic aneurysm, which currently have limited treatment options beyond surgery.
