Vitamin D deficiency has been associated with human abdominal aortic aneurysm (AAA) however its role in AAA pathogenesis is unclear. The aim of this 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 deficient through dietary restriction and during AngII infusion developed larger AAAs as assessed by ultrasound and ex vivo morphometry which 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 upregulation 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 hours induced upregulation of sclerostin (P<0.001) and changed the expression of a range of other genes important in extracellular matrix remodeling. This 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.
Vitamin D deficiency promotes large rupture-prone abdominal aortic aneurysms and cholecalciferol supplementation limits progression of aneurysms in a mouse model
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Vianne Nsengiyumva, Smriti M Krishna, Corey S Moran, Joseph V Moxon, Susan Morton, Michael Clarke, Sai-Wang Seto, Jonathan Golledge; Vitamin D deficiency promotes large rupture-prone abdominal aortic aneurysms and cholecalciferol supplementation limits progression of aneurysms in a mouse model. Clin Sci (Lond) CS20200980. doi: https://doi.org/10.1042/CS20200980
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