b-Carotene Attenuates Angiotensin II-Induced Aortic Aneurysm by Alleviating Macrophage Recruitment in Apoe2/2 Mice

Abdominal aortic aneurysm (AAA) is a common chronic degenerative disease characterized by progressive aortic dilation and rupture. The mechanisms underlying the role of a-tocopherol and b-carotene on AAA have not been comprehensively assessed. We investigated if a-tocopherol and b-carotene supplementation could attenuate AAA, and studied the underlying mechanisms utilized by the antioxidants to alleviate AAA. Four-months-old Apoe2/2 mice were used in the induction of aneurysm by infusion of angiotensin II (Ang II), and were orally administered with a-tocopherol and b-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 (2.2460.20 mm) in the aneurysm-induced animals as compared to control mice (1.1760.06 mm). Interestingly, b-carotene dramatically controlled the diffusion of macrophages into the aortic tunica intima, and circulation. It also dissolved the formation of atheromatous plaque. Further, b-carotene significantly decreased the aortic diameter (1.3360.12 mm) in the aneurysm-induced mice (b-carotene, P = 0.0002). It also downregulated ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9, MMP-12, PPAR-a and PPAR-c following treatment. Hence, dietary supplementation of b-carotene may have a protectiv