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TGF-β activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II-infused mice
- Source :
- Journal of Clinical Investigation. February, 2010, Vol. 120 Issue 2, p422, 11 p.
- Publication Year :
- 2010
-
Abstract
- Complicated abdominal aortic aneurysm (AAA) is a major cause of mortality in elderly men. Ang II-dependent TGF-β activity promotes aortic aneurysm progression in experimental Marfan syndrome. However, the role of TGF-β in experimental models of AAA has not been comprehensively assessed. Here, we show that systemic neutralization of TGF-β activity breaks the resistance of normocholesterolemic C57BL/6 mice to Ang II-induced AAA formation and markedly increases their susceptibility to the disease. These aneurysms displayed a large spectrum of complications on echography, including fissuration, double channel formation, and rupture, leading to death from aneurysm complications. The disease was refractory to inhibition of IFN-γ, IL-4, IL-6, or TNF-α signaling. Genetic deletion of T and B cells or inhibition of the CX3CR1 pathway resulted in partial protection. Interestingly, neutralization of TGF-β activity enhanced monocyte invasiveness, and monocyte depletion markedly inhibited aneurysm progression and complications. Finally, TGF-β neutralization increased MMP-12 activity, and MMP-12 deficiency prevented aneurysm rupture. These results clearly identify a critical role for TGF-β in the taming of the innate immune response and the preservation of vessel integrity in C57BL/6 mice, which contrasts with its reported pathogenic role in Marfan syndrome.<br />Introduction Abdominal aortic aneurysm (AAA) is an age-associated disease that affects approximately 5% of elderly men and is responsible for a significant number of deaths in Western countries (1). At [...]
- Subjects :
- Immune response -- Physiological aspects -- Health aspects
Aortic aneurysms -- Complications and side effects -- Development and progression -- Patient outcomes
Transforming growth factors -- Health aspects -- Physiological aspects
Angiotensin -- Complications and side effects -- Dosage and administration -- Health aspects -- Physiological aspects
Health care industry
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 120
- Issue :
- 2
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.241872626
- Full Text :
- https://doi.org/10.1172/JCI38136