β-Carotene Attenuates Angiotensin II-Induced Aortic Aneurysm by Alleviating Macrophage Recruitment in Apoe(-/-) Mice

PLoS One. 2013 Jun 27;8(6):e67098. doi: 10.1371/journal.pone.0067098. Print 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II
  • Animals
  • Antioxidants / administration & dosage
  • Aorta, Abdominal / immunology
  • Aorta, Abdominal / pathology
  • Aortic Aneurysm, Abdominal / diet therapy*
  • Aortic Aneurysm, Abdominal / immunology
  • Aortic Aneurysm, Abdominal / pathology
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Cholesterol, LDL / metabolism
  • Dietary Supplements*
  • Disease Models, Animal
  • Lymphocytes / metabolism
  • Lymphocytes / pathology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Male
  • Mice, Knockout
  • Organ Size
  • Plaque, Atherosclerotic / diet therapy
  • Plaque, Atherosclerotic / immunology
  • Plaque, Atherosclerotic / pathology
  • alpha-Tocopherol / administration & dosage*
  • beta Carotene / administration & dosage*

Substances

  • Antioxidants
  • Apolipoproteins E
  • Cholesterol, LDL
  • beta Carotene
  • Angiotensin II
  • alpha-Tocopherol

Grant support

This work was supported by the Indian Council of Medical Research, Government of India (Project IRIS ID. 2005-04430). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.