Aortic & peripheral vascular disease
Hypertriglyceridemia as a Key Contributor to Abdominal Aortic Aneurysm Development and Rupture: Insights From Genetic and Experimental Models
Authors' conclusion
These findings identify hypertriglyceridemia as a key contributor to AAA pathogenesis
Study context
- Population
- Mendelian randomization of abdominal aortic aneurysm (AAA) risk; hypertriglyceridemic mouse models (Lpl-deficient, Apoa5-deficient, human APOC3 transgenic) in the angiotensin II infusion AAA model
Methodological detailsMendelian randomization, mouse models
- Mendelian randomization
- Mouse models
Main finding
As reported in the abstract
- MR: causal relationships between elevated TG-rich lipoproteins, TG metabolism-related proteins/metabolites and AAA risk
- Lpl-deficient mice (severely elevated TG): most died of aortic rupture
- Apoa5-deficient mice (moderately elevated TG): accelerated AAA
- Human APOC3 transgenic mice (dramatically elevated TG): aortic dissection and rupture
- Elevated TG and palmitate inhibited lysyl oxidase (LOX) maturation and reduced LOX activity
- Local LOX overexpression eliminated the proaneurysmal effect of hypertriglyceridemia in human APOC3 transgenic mice
- Angptl3-targeting antisense oligonucleotide profoundly attenuated AAA progression in human APOC3 transgenic and Apoe-deficient mice
Original publication
Hypertriglyceridemia as a Key Contributor to Abdominal Aortic Aneurysm Development and Rupture: Insights From Genetic and Experimental Models. Circulation. Published 5 August 2025. doi:10.
Summarised from the published abstract; every number is checked against it