Open AccessDisruption of Osteoprotegerin has complex effects on medial destruction and adventitial fibrosis during mouse abdominal aortic aneurysm formation
Author(s) -
Bumdelger Batmunkh,
Mikage Otani,
Kohei Karasaki,
Chiemi Sakai,
Mari Ishida,
Hiroki Kokubo,
Masao Yoshizumi
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0235553
Subject(s) - adventitia , osteoprotegerin , medicine , abdominal aortic aneurysm , aneurysm , aortic aneurysm , aorta , apolipoprotein e , myofibroblast , angiotensin ii , fibrosis , arteriosclerosis , pathology , cardiology , anatomy , surgery , receptor , disease , activator (genetics)
Aortic aneurysm refers to dilatation of the aorta due to loss of elasticity and degenerative weakening of its wall. A preventive role for osteoprotegerin (Opg) in the development of abdominal aortic aneurysm has been reported in the CaCl 2 -induced aneurysm model, whereas Opg was found to promote suprarenal aortic aneurysm in the AngII-induced ApoE knockout mouse aneurysm model. To determine whether there is a common underlying mechanism to explain the impact of Opg deficiency on the vascular structure of the two aneurysm models, we analyzed suprarenal aortic tissue of 6-month-old ApoE -/- Opg -/- mice after AngII infusion for 28 days. Less aortic dissection and aortic lumen dilatation, more adventitial thickening, and higher expression of collagen I and Trail were observed in ApoE -/- Opg -/- mice relative to ApoE -/- Opg +/+ mice. An accumulation of α-smooth muscle actin and vimentin double-positive myofibroblasts was noted in the thickened adventitia of ApoE -/- Opg -/- mice. Our results suggest that fibrotic remodeling of the aorta induced by myofibroblast accumulation might be an important pathological event which tends to limit AngII-induced aortic dilatation in ApoE -/- Opg -/- mice.