Abstract
Objective: Copper deficiency (CD) has been linked to impaired collagen synthesis and the development of abdominal aortic aneurysms (AAA) in swine. This study sought to evaluate the effect of a CD diet on a porcine AAA model.Methods: A CD diet was fed to Yorkshire swine for 3mths. In CD and regular‐fed (RF) swine the infrarenal aorta was balloon dilated and infused with collagenase/elastase (16000U/1000U) (Fig 1). At 2wks, control (suprarenal aorta) and AAA tissues were frozen in liquid nitrogen and pulverized for RNA extraction. RNA from 3 CD and 3 RF samples was biotin‐labeled and hybridized to porcine arrays (20,201 genes). Relative gene intensities equaled log2(AAA/control). A 2‐class unpaired Significance Analysis of Microarray (Fig 2) test was conducted, false discovery rate (FDR) < 2.2%.Results: 55 genes were downregulated and 20 genes were upregulated in CD compared to RF swine (Fig 3). Diminished expression of heme oxygenase and thymidilate synthetase was consistent with vascular smooth muscle and endothelial dysregulation. Differential expression of MHC classes I/II was consistent with an autoimmune etiology for AAA. Inflammatory pathology was supported by altered expressions of cytochrome P450, oligoadenylate synthetase and sphingosine kinase.Conclusion: The addition of a CD diet to the porcine AAA model introduced novel links to known AAA connective tissue biology.Support: NIH‐K08HL073313
Published Version
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