title: High-fat diet- and angiotensin II-induced aneurysm concurrently elicits splenic hypertrophy.
abstract: BACKGROUND
  Angiotensin II (Ang II) and high-fat diet are implicated in causing pathological changes in the vascular endothelium, brain, kidney and liver. The association of aneurysm leading to histopathological changes in the splenic compartment remains elusive. Further, the salubrious credentials of antioxidants, especially α-tocopherol and β-carotene in the resolution of splenic pathology have not been investigated.
  
  
  METHODS
  Four-month-old Apoe(-/-) mice were used in the induction of aneurysm by infusing Ang II, and subsequently were orally administered with α-tocopherol and β-carotene-enriched diet for 60 days.
  
  
  RESULTS
  We observed splenomegaly in Ang II-infused aneurysm and high-fat diet-supplemented mice as compared to normal mice. These observations were further confirmed through histopathological investigations, demonstrating splenic follicular hypertrophy. We observed a remarkable decrease in the size of spleen in α-tocopherol and β-carotene-treated Apoe(-/-) mice as compared with Ang II-treated animals. Furthermore, no marked changes in the histopathological splenic sections were seen in the β-carotene-treated group. However, hyperplasia and proliferation of immature lymphocytes in the follicles were observed in the α-tocopherol-treated animals. We found that CD4+ T-cell levels were increased in the high-fat diet group relative to the control group and were decreased in the β-carotene-treated animals.
  
  
  CONCLUSIONS
  Our study provides evidence that Ang II infusion and high-fat supplementation induces abdominal aortic aneurysm that has pathological implications to the spleen. The use of β-carotene but not α-tocopherol as an antioxidant markedly ameliorates the pathological changes in spleen.
authors.affiliation: Center for Cellular and Molecular Biology (CCMB), Hyderabad, India; Department of Orthopaedic Surgery, National Orthopaedics Center for Excellence in Research and Learning (NOCERAL), 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: Esaki M
authors.initials: EM
authors.lastname: Shankar
authors.forename: Tunku
authors.initials: T
authors.lastname: Kamarul
authors.forename: Jerald M
authors.initials: JM
authors.lastname: Kumar
mesh_terms: D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology*; D001057:Apolipoproteins E / Q000172:deficiency; D059305:Diet, High-Fat / Q000009:adverse effects*; D019587:Dietary Supplements / Q000009:adverse effects; D008297:Male; D018345:Mice, Knockout; D013163:Splenomegaly / Q000209:etiology*; D013601:T-Lymphocytes / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000633:toxicity*; D024502:alpha-Tocopherol / Q000494:pharmacology; D019207:beta Carotene / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D014662:Vasoconstrictor Agents; D019207:beta Carotene; D000804:Angiotensin II; D024502:alpha-Tocopherol
keywords: Aneurysm; angiotensin II; antioxidants; spleen; β-carotene