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.

High‐fat diet‐ and angiotensin II‐induced aneurysm concurrently elicits splenic hypertrophy

“…The present study demonstrates this very clearly, with marked splenomegaly observed in all Ang II‐treated mice. It has been suggested that this may be the eventual outcome as the result of ongoing hepatic inflammation in the AAA scenario . However, we cannot also exclude the fact that inflammatory mediators could be one of the likely causes of the splenic pathology observed.…”

“…This assumption has been supported in several lab models where the infusion of Ang‐II resulted in the induction of AAA in Apoe −/− mice . Ang II and high‐fat diet have been implicated in causing pathological changes in the vascular endothelium, brain, kidney and liver . The association between pathologies occurring in visceral organs with secondary pathology related to arterial aneurysm has rarely been documented.…”

“…Antioxidants, especially α‐tocopherol (vitamin E), β‐carotene and C‐phycocyanin have strong free radical scavenging properties . β‐carotene supplementation has been shown to dramatically control the diffusion of inflammatory macrophages into the aortic tunica intima, and circulating macrophages in addition to resolving the formation of atheromatous plaque in experimental aneurysm . Due to this, antioxidants are currently being used in the treatment of oxidative stress‐related ailments especially atherosclerosis , cardiovascular and kidney diseases, and type I diabetes.…”

Metformin Inhibits Monocyte-to-Macrophage Differentiation via AMPK-Mediated Inhibition of STAT3 Activation: Potential Role in Atherosclerosis

“…Animals were randomly divided into three groups of 12: 1) control, 2) Ang-II treatment, and 3) Ang-II + metformin treatment. Ang-II and metformin treatment groups received Ang-II (Sigma) at a dose of 1.44 mg/kg/day as described previously (16)(17)(18) for 6 weeks through a subcutaneous route, whereas the control group received normal saline. The metformin treatment group received the drug at a dose of 100 mg/kg/day in normal drinking water.…”

Effect of beta-carotene on titanium oxide nanoparticles-induced testicular toxicity in mice

“…BC possesses a wide array of pharmacological and biological activities including: antioxidant, radioprotective, cardiovascular protection, antiepilepsy [15][16][17][18][19]. Previous studies have demonstrated protective action of BC against some toxicants including Fenvalerate, metotroxate and Cadmium [20][21][22].…”