Abstract
Abdominal aortic aneurysm (AAA) is a common chronic degenerative disease characterized by progressive aortic dilation and rupture. The mechanisms underlying the role of α-tocopherol and β-carotene on AAA have not been comprehensively assessed. We investigated if α-tocopherol and β-carotene supplementation could attenuate AAA, and studied the underlying mechanisms utilized by the antioxidants to alleviate AAA. Four-months-old Apoe−/− mice were used in the induction of aneurysm by infusion of angiotensin II (Ang II), and were orally administered with α-tocopherol and β-carotene enriched diet for 60 days. Significant increase of LDL, cholesterol, triglycerides and circulating inflammatory cells was observed in the Ang II-treated animals, and gene expression studies showed that ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9 and MMP-12 were upregulated in the aorta of aneurysm-induced mice. Extensive plaques, aneurysm and diffusion of inflammatory cells into the tunica intima were also noticed. The size of aorta was significantly (P = 0.0002) increased (2.24±0.20 mm) in the aneurysm-induced animals as compared to control mice (1.17±0.06 mm). Interestingly, β-carotene dramatically controlled the diffusion of macrophages into the aortic tunica intima, and circulation. It also dissolved the formation of atheromatous plaque. Further, β-carotene significantly decreased the aortic diameter (1.33±0.12 mm) in the aneurysm-induced mice (β-carotene, P = 0.0002). It also downregulated ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9, MMP-12, PPAR-α and PPAR-γ following treatment. Hence, dietary supplementation of β-carotene may have a protective function against Ang II-induced AAA by ameliorating macrophage recruitment in Apoe−/− mice.
Highlights
Abdominal aortic aneurysm (AAA) is a common chronic degenerative disease involving the aortic wall in human
Angiotensin II Induces Aneurysm by the Upregulation of matrix metalloproteinases (MMPs), peroxisome proliferatoractivated receptors (PPARs)-c, macrophage chemotactic protein-1 (MCP-1) and uPAR mRNA Expression Given the role of adhesion molecules in the pathogenesis of atherosclerosis, we investigated the effect of intercellular adhesion molecule-1 (ICAM-1) and VCAM1 in our present analysis
We have convincingly demonstrated that dietary supplementation of a-tocopherol and b-carotene resulted in substantial protection of Apoe2/2 mice from AAA
Summary
Abdominal aortic aneurysm (AAA) is a common chronic degenerative disease involving the aortic wall in human. Recent lines of evidence suggest that Ang II could trigger intracellular accumulation of reactive oxygen species (ROS) culminating in the initiation of lipid peroxidation-mediated oxidative stress [5]. Substantial experimental evidence suggests that ROS could induce the expression of certain matrix metalloproteinases (MMPs) [7], plasma soluble adhesion molecules e.g. intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), activation of chemokines, e.g. macrophage chemotactic protein-1 (MCP-1) and macrophagecolony stimulating factor (M-CSF), contributing to the onset of vascular inflammation [2,3]. It is sufficiently evident that lipid peroxidation and transcriptional factors play a major role in determining the onset of atherosclerosis, potential therapeutic targets against AAA still remain controversial. Open surgical repair can markedly improve disease prognosis in patients with large AAAs, invasive surgical procedures and associated complications are critical limiting factors, especially in old age [1]
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