Vitamin D deficiency promotes large rupture-prone abdominal aortic aneurysms and cholecalciferol supplementation limits progression of aneurysms in a mouse model. Issue 18 (29th September 2020)

• Record Type: Journal Article
• Authors: Nsengiyumva, Vianne; Krishna, Smriti M.; Moran, Corey S.; Moxon, Joseph V.; Morton, Susan K.; Clarke, Michael W.; Seto, Sai-Wang; Golledge, Jonathan
• Is Part Of: Clinical science. Volume 134:Issue 18(2020)
• Page Start: 2521
• Page End: 2534
• Publication Date: 2020-09-29
• Subjects: Abdominal aortic aneurysm -- sclerostin -- vitamin D; Medicine -- Periodicals; Biochemistry -- Periodicals; 616
• DOI: 10.1042/CS20200980
• Languages: English
• ISSNs: 0143-5221

Abstract

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.