title: β-Carotene Attenuates Angiotensin II-Induced Aortic Aneurysm by Alleviating Macrophage Recruitment in Apoe(-/-) Mice.
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.
authors.affiliation: Center for Cellular and Molecular Biology, Hyderabad, India ; Department of Orthopedics, National Orthopaedics Center for Excellence in Research and Learning, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kaliappan
authors.initials: K
authors.lastname: Gopal
authors.forename: Perumal
authors.initials: P
authors.lastname: Nagarajan
authors.forename: Jose
authors.initials: J
authors.lastname: Jedy
authors.forename: Avinash T
authors.initials: AT
authors.lastname: Raj
authors.forename: S Kalai
authors.initials: SK
authors.lastname: Gnanaselvi
authors.forename: Parveen
authors.initials: P
authors.lastname: Jahan
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Sharma
authors.forename: Esaki M
authors.initials: EM
authors.lastname: Shankar
authors.forename: Jerald M
authors.initials: JM
authors.lastname: Kumar
mesh_terms: D000804:Angiotensin II; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001012:Aorta, Abdominal / Q000276:immunology / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000178:diet therapy* / Q000276:immunology / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D008078:Cholesterol, LDL / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018345:Mice, Knockout; D009929:Organ Size; D058226:Plaque, Atherosclerotic / Q000178:diet therapy / Q000276:immunology / Q000473:pathology; D024502:alpha-Tocopherol / Q000008:administration & dosage*; D019207:beta Carotene / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D019207:beta Carotene; D000804:Angiotensin II; D024502:alpha-Tocopherol