High Triglyceride Levels Linked to Dangerous Abdominal Aortic Aneurysms in Mouse Study

A recent study conducted by researchers at Michigan Medicine has established a direct connection between elevated triglyceride levels and the development of life-threatening abdominal aortic aneurysms. Triglycerides, a common form of fat found in the body and consumed through diet, have traditionally been viewed as biomarkers for vascular disease. However, this research demonstrates that they actively contribute to the progression and rupture of aneurysms.

The study involved multiple mouse models with hypertriglyceridemia, revealing that increased triglyceride levels have a dose-dependent effect, accelerating aneurysm formation and advancing the risk of aortic dissection. Researchers identified triglyceride-rich lipoproteins and key regulatory proteins like APOC3 and ANGPTL3 as causal factors in aneurysm development.

Further investigation uncovered that high triglycerides impair the function of lysyl oxidase (LOX), an enzyme crucial for maintaining the structural integrity of the aortic wall. This enzyme dysfunction weakens connective tissue, facilitating aneurysm growth and rupture. Overexpressing LOX in mouse models effectively countered these effects, validating the mechanism.

Standard lipid-lowering medications such as niacin did not sufficiently reduce triglycerides to protective levels. Instead, experimental antisense oligonucleotide therapy targeting ANGPTL3 showed promise. This treatment significantly lowered triglycerides by up to 50%, preventing aneurysm formation and dissection in the models.

Lead author Eugene Chen emphasizes the clinical significance: "Our findings suggest that managing triglycerides could become a transformative approach in preventing and treating abdominal aortic aneurysms, especially since current options are limited mostly to surgical repair." Co-senior author Yanhong Guo highlighted the potential for future therapies to address at-risk populations, marking a possible shift in vascular disease management.

This groundbreaking research challenges prevailing perceptions and opens new pathways for pharmacological interventions aimed at reducing aneurysm-related complications. The full study is published in Circulation.