Angiopoietin-2 attenuates angiotensin II-induced aortic aneurysm and atherosclerosis in apolipoprotein E-deficient mice

Yu, Hongyou, Moran, Corey S., Trollope, Alexandra F., Woodward, Lynn, Kinobe, Robert, Rush, Catherine M., and Golledge, Jonathan (2016) Angiopoietin-2 attenuates angiotensin II-induced aortic aneurysm and atherosclerosis in apolipoprotein E-deficient mice. Scientific Reports, 6. 35190 . pp. 1-11.

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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.

Item ID: 46154
Item Type: Article (Research - C1)
ISSN: 2045-2322
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© The Author(s) 2016.

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Funders: National Health and Medical Research Council (NHMRC), Queensland Government (QG)
Projects and Grants: NHMRC 1021416, NHMRC 1003707, NHMRC 540405, NHMRC 1000967, NHMRC Practitioner Fellowship 1019921, QG Senior Clinical Research Fellowship
Date Deposited: 23 Oct 2016 23:50
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320101 Cardiology (incl. cardiovascular diseases) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%
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