Vitamin D deficiency promotes large rupture-prone abdominal aortic aneurysms and cholecalciferol supplementation limits progression of aneurysms in a mouse model
Nsengiyumva V, Krishna SM, Moran CS, Moxon JV, Morton SK, Clarke MW, Seto SW, Golledge J
Clinical science (London, England : 1979) · 18 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Government
- Queensland Government
- Government
- Medical Research Council
- Government
- National Health and Medical Research Council
- Grants
- National Health and Medical Research Council (1117061); National Health and Medical Research Council (1079193); National Health and Medical Research Council (1098717)
Based on 3 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2020-09-01 · Clin Sci (Lond) · vol. 134 · issue 18 · pp. 2521–2534
- Publisher
- Portland Press
- Cited
- 25 citations · more than 85% of similar papers · 1.4× the field average
- References
- 28 works
- Access
- Open access (hybrid journal) · CC-BY-NC-ND
- Research areas
- Aortic aneurysm repair treatments · Cardiac, Anesthesia and Surgical Outcomes · Connective tissue disorders research
- Keywords
- vitamin D deficiency, Endocrinology, Medicine, Vitamin D and neurology, Internal medicine, Cholecalciferol, Angiotensin II, Vitamin, Blood pressure
- MeSH
- muscle, smooth, vascular, aorta, abdominal, myocytes, smooth muscle, animals, mice, inbred c57bl, mice, knockout, humans, aortic rupture, aortic aneurysm, abdominal, vitamin d deficiency, disease models, animal, disease progression, cholecalciferol, adaptor proteins, signal transducing, angiotensin ii, apolipoproteins e, caloric restriction, gene expression regulation, up-regulation, blood pressure, dietary supplements
8 authors
From AU, HK
- Vianne NsengiyumvaJames Cook University
- Smriti Murali KrishnaJames Cook University
- Corey Stephen MoranJames Cook University
- Joseph Vaughan MoxonJames Cook University
- Susan K. MortonJames Cook University
- Michael W. ClarkeThe University of Western Australia
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-ND).
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