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.
Highlights
Humans, increased serum Angpt[2] is associated with Abdominal aortic aneurysm (AAA) prevalence and cardiovascular mortality in older men[13], a direct role for Angpt[2] in AAA remains unclear
A total of 50 6-month-old male ApoE−/− mice were infused with angiotensin II (AngII) for 14 days
This study investigated the effect of Angpt[2] on AAA development and atherosclerosis in the ApoE−/− mouse model
Summary
Humans, increased serum Angpt[2] is associated with AAA prevalence and cardiovascular mortality in older men[13], a direct role for Angpt[2] in AAA remains unclear. Given the significance of angiogenesis and inflammation in AAA and atherosclerosis, we hypothesised that Angpt[2] would be important in the development of AAA and atherosclerosis and examined this in the angiotensin II (AngII)-infused Apolipoprotein E deficient (ApoE−/−) mouse model
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