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Updated: Sep 12, 2025
06:08
Ultrasound Imaging of the Thoracic and Abdominal Aorta in Mice to Determine Aneurysm Dimensions
Published on: March 8, 2019
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Hypertriglyceridemia as a Key Contributor to Abdominal Aortic Aneurysm Development and Rupture: Insights From Genetic
Yaozhong Liu1, Huilun Wang1,2, Minzhi Yu3
1Frankel Cardiovascular Center, Department of Internal Medicine (Y.L., H.W., Ying Zhao, Y.C., Y.D., Yang Zhao, X.W., G.Z., C.X., H. Liu, I.S., L.C., J.Z., Y.E.C., Y.G.), University of Michigan Medical Center, Ann Arbor.
Circulation
|August 5, 2025
Summary
High triglycerides accelerate abdominal aortic aneurysm (AAA) development. Targeting triglyceride-rich lipoproteins offers a potential therapeutic strategy for this life-threatening vascular disease.
Area of Science:
- Cardiovascular Research
- Vascular Biology
- Metabolic Syndrome
Background:
- Abdominal aortic aneurysm (AAA) is a dangerous vascular condition lacking effective drug treatments.
- The role of triglycerides (TGs) in AAA development is not well understood.
- Current research aims to clarify the link between TGs and AAA pathogenesis.
Purpose of the Study:
- To investigate the causal relationship between triglycerides and abdominal aortic aneurysm (AAA) risk.
- To explore the mechanistic pathways linking hypertriglyceridemia to AAA.
- To evaluate the therapeutic potential of targeting triglyceride metabolism in AAA.
Main Methods:
- Mendelian randomization analysis integrating genetic, proteomic, and metabolomic data.
- Utilized mouse models with genetic modifications leading to hypertriglyceridemia (Lpl-deficient, Apoa5-deficient, APOC3 transgenic mice).
- Conducted mechanistic studies involving cell culture (palmitate treatment) and in vivo gene manipulation, including antisense oligonucleotide therapy.
Main Results:
- Mendelian randomization confirmed a causal link between elevated TG-rich lipoproteins and AAA risk.
- Hypertriglyceridemia accelerated AAA development, leading to aortic rupture in mouse models.
- Elevated TGs impaired lysyl oxidase (LOX) maturation and activity, a key factor in aortic integrity.
- Therapeutic reduction of TGs using an Angptl3-targeting antisense oligonucleotide attenuated AAA progression.
Conclusions:
- Hypertriglyceridemia is a significant contributor to the development of abdominal aortic aneurysms.
- Targeting triglyceride-rich lipoproteins represents a promising therapeutic avenue for AAA treatment.
- Further research into TG metabolism pathways could yield novel strategies for preventing and managing AAA.
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