title: Angiopoietin-2 attenuates angiotensin II-induced aortic aneurysm and atherosclerosis in apolipoprotein E-deficient mice.
abstract: Angiogenesis and inflammation are implicated in aortic aneurysm and atherosclerosis and regulated by angiopoietin-2 (Angpt2). The effect of Angpt2 administration on experimental aortic aneurysm and atherosclerosis was examined. Six-month-old male apolipoprotein E deficient (ApoE-/-) mice were infused with angiotensin II (AngII) and administered subcutaneous human Fc-protein (control) or recombinant Angpt2 (rAngpt2) over 14 days. Administration of rAngpt2 significantly inhibited AngII-induced aortic dilatation and rupture of the suprarenal aorta (SRA), and development of atherosclerosis within the aortic arch. These effects were blood pressure and plasma lipoprotein independent and associated with Tie2 activation and down-regulation of monocyte chemotactic protein-1 (MCP-1) within the SRA. Plasma concentrations of MCP-1 and interleukin-6 were significantly lower in mice receiving rAngpt2. Immunostaining for the monocyte/macrophage marker MOMA-2 and the angiogenesis marker CD31 within the SRA were less in mice receiving rAngpt2 than controls. The percentage of inflammatory (Ly6Chi) monocytes within the bone marrow was increased while that in peripheral blood was decreased by rAngpt2 administration. In conclusion, administration of rAngpt2 attenuated angiotensin II-induced aortic aneurysm and atherosclerosis in ApoE-/-mice associated with reduced aortic inflammation and angiogenesis. Up-regulation of Angpt2 may have potential therapeutic value in patients with aortic aneurysm and atherosclerosis.
authors: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, 4811, Australia.
authors: Hongyou
authors: H
authors: Yu
authors: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, 4811, Australia.
authors: Corey S
authors: CS
authors: Moran
authors: Discipline of Anatomy, College of Medicine and Dentistry, James Cook University, Townsville, 4811, Australia.
authors: Alexandra F
authors: AF
authors: Trollope
authors: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, 4811, Australia.
authors: Lynn
authors: L
authors: Woodward
authors: Discipline of Biomedicine, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, 4811, Australia.
authors: Robert
authors: R
authors: Kinobe
authors: Discipline of Biomedicine, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, 4811, Australia.
authors: Catherine M
authors: CM
authors: Rush
authors: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, 4811, Australia.|Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, 4814, Australia.
authors: Jonathan
authors: J
authors: Golledge
mesh_terms: D042702:Angiopoietin-2 / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000517:prevention & control*; D050197:Atherosclerosis / Q000235:genetics / Q000517:prevention & control*; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D000074085:Mice, Knockout, ApoE; D018919:Neovascularization, Physiologic / Q000502:physiology*; D042787:Receptor, TIE-2 / Q000378:metabolism
chemical_list: D042702:Angiopoietin-2; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; C577686:interleukin-6, mouse; D000804:Angiotensin II; D042787:Receptor, TIE-2; C079086:Tek protein, mouse