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Macrophage elastase derived from adventitial macrophages modulates aortic remodeling.
Yajie Chen1,2, Xiawen Yang1, Shuji Kitajima3
1Guangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China.
Frontiers in Cell and Developmental Biology
|January 27, 2023
Summary
Adventitial inflammation and increased matrix metalloproteinase-12 (MMP-12) from macrophages significantly worsen abdominal aortic aneurysm (AAA) development and aortic remodeling in rabbits. This highlights MMP-12
Area of Science:
- Vascular Biology
- Immunology
- Pathology
Background:
- Abdominal aortic aneurysm (AAA) involves atherosclerosis, medial elastic tissue disruption, and adventitial inflammation.
- The role of adventitial inflammatory macrophages in AAA pathogenesis is not fully understood.
- Matrix metalloproteinase-12 (MMP-12) from macrophages is implicated in atherosclerosis and AAA.
Purpose of the Study:
- To investigate the impact of adventitial macrophage accumulation and MMP-12 expression on aortic remodeling in a rabbit AAA model.
- To compare aortic lesions in transgenic rabbits overexpressing MMP-12 with non-transgenic controls.
Main Methods:
- Developed a carrageenan-induced abdominal aortic adventitial inflammation model in hypercholesterolemic rabbits.
- Utilized transgenic (Tg) rabbits with high macrophage-derived MMP-12 expression versus non-Tg rabbits.
- Analyzed aortic medial and adventitial lesions, elastic lamellae destruction, and lumen dilation using RT-PCR and Western blotting.
Main Results:
- Tg rabbits showed significantly greater aortic medial and adventitial lesions compared to non-Tg rabbits.
- Increased macrophage infiltration and prominent elastic lamellae destruction were observed in Tg rabbits.
- Elevated MMP-12, MMP-2, and MMP-3 levels correlated with increased macrophage numbers and aortic dilation in Tg rabbits.
Conclusions:
- Adventitial inflammation is a key driver of aortic remodeling in AAA development.
- Increased MMP-12 expression by adventitial macrophages plays a critical role in AAA pathogenesis.
- Targeting adventitial macrophage-derived MMP-12 may offer therapeutic strategies for vascular diseases like AAA.
