Abstract 14000: ApoB-100 Related Peptide Vaccine Reduces Hypertension and Mortality in a Model of Angiotensin II-Induced Aortic Aneurysm in Apo E (-/-) Mice: A Novel Therapeutic Paradigm
Background: Aortic aneurysms (AA) are characterized by increased oxidative stress with chronic immune-mediated inflammation of the aortic wall. We recently demonstrated that immunization with apoB-100 related peptide p210 reduces atherosclerosis with favorable modulation of immune system in apoE (-/-) mice. We hypothesized that the p210 vaccine would significantly reduce angiotensin II (AngII)-induced AA rupture related mortality in apoE (-/-) mice.
Method and Results: ApoE (-/-) mice were immunized with p210/cBSA/Alum (p210; 100 g) at 7, 10, and 12 weeks of age. Mice receiving PBS or cBSA/Alum (cBSA) served as controls. At 10 weeks of age, mice were subcutaneously implanted with an osmotic pump which released AngII (1 mg/Kg/min), and were euthanized 4 weeks later. The aorta, spleen, and lymph nodes (LN) were harvested. The p210 vaccine significantly reduced mortality due to AA rupture compared to controls (Figure). Flow cytometric analysis of dendritic cells (DCs) in LNs and spleen showed intracellular IFN-gamma expression was upregulated in the p210 group. Aortic superoxide production measured by in situ dihydroethidium method and aortic AT1 receptor (AT1R) expression measured by Western blot were significantly decreased in p210 group. The p210 vaccine significantly decreased mean arterial BP at 13 weeks of age (see Table for all data).
Conclusion: Mortality from AngII induced AA rupture was significantly reduced by the p210 vaccine. This protective effect was associated with upregulation of IFN-gamma expression in DCs and decreased arterial BP, AT1R expression, and superoxide production in aorta. The vaccine may be a promising new non-invasive treatment for AA. Figure
- © 2011 by American Heart Association, Inc.