Back to Search
Start Over
Vitamin D deficiency promotes large rupture-prone abdominal aortic aneurysms and cholecalciferol supplementation limits progression of aneurysms in a mouse model.
- Source :
-
Clinical science (London, England : 1979) [Clin Sci (Lond)] 2020 Sep 30; Vol. 134 (18), pp. 2521-2534. - Publication Year :
- 2020
-
Abstract
- Vitamin D deficiency has been associated with human abdominal aortic aneurysm (AAA); however, its role in AAA pathogenesis is unclear. The aim of the present study was to investigate the effect of vitamin D deficiency on AAA development and examine if administering cholecalciferol (CCF) could limit growth of established AAA within the angiotensin-II (AngII) infused apolipoprotein E-deficient mouse model. Mice were rendered vitamin D deficiency through dietary restriction and during AngII infusion developed larger AAAs as assessed by ultrasound and ex vivo morphometry that ruptured more commonly (48% vs. 19%; P=0.028) than controls. Vitamin D deficiency was associated with increased aortic expression of osteopontin and matrix metalloproteinase-2 and -9 than controls. CCF administration to mice with established aortic aneurysms limited AAA growth as assessed by ultrasound (P<0.001) and ex vivo morphometry (P=0.036) and reduced rupture rate (8% vs. 46%; P=0.031). This effect was associated with up-regulation of circulating and aortic sclerostin. Incubation of human aortic smooth muscle cells with 1,25-dihyroxyvitamin D3 (the active metabolite of vitamin D) for 48 h induced up-regulation of sclerostin (P<0.001) and changed the expression of a range of other genes important in extracellular matrix remodeling. The present study suggests that vitamin D deficiency promotes development of large rupture-prone aortic aneurysms in an experimental model. CCF administration limited both growth and rupture of established aneurysms. These effects of vitamin D appeared to be mediated via changes in genes involved in extracellular matrix remodeling, particularly sclerostin.<br /> (© 2020 The Author(s).)
- Subjects :
- Adaptor Proteins, Signal Transducing metabolism
Angiotensin II
Animals
Aorta, Abdominal drug effects
Aorta, Abdominal metabolism
Aorta, Abdominal pathology
Aorta, Abdominal physiopathology
Aortic Aneurysm, Abdominal physiopathology
Aortic Rupture physiopathology
Apolipoproteins E deficiency
Blood Pressure drug effects
Caloric Restriction
Cholecalciferol pharmacology
Disease Models, Animal
Gene Expression Regulation drug effects
Humans
Mice, Inbred C57BL
Mice, Knockout
Muscle, Smooth, Vascular pathology
Myocytes, Smooth Muscle drug effects
Myocytes, Smooth Muscle metabolism
Up-Regulation drug effects
Vitamin D Deficiency physiopathology
Aortic Aneurysm, Abdominal drug therapy
Aortic Aneurysm, Abdominal etiology
Aortic Rupture drug therapy
Aortic Rupture etiology
Cholecalciferol therapeutic use
Dietary Supplements
Disease Progression
Vitamin D Deficiency complications
Subjects
Details
- Language :
- English
- ISSN :
- 1470-8736
- Volume :
- 134
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Clinical science (London, England : 1979)
- Publication Type :
- Academic Journal
- Accession number :
- 32936248
- Full Text :
- https://doi.org/10.1042/CS20200980