Abstract 18473: ApoB-100 Related Peptide Immunization Confers Protection Against Angiotension II-induced Renal Inflammatory Responses
Background: T cells play an important role in angiotensin II (AngII)-induced hypertension and aneurysm formation. Inflammatory responses, typified by reactive oxygen species (ROS) and Interleukin-6 (IL-6), are involved in AngII-induced hypertension and renal damage. We recently demonstrated that immunization with apoB-100 related peptide p210 reduced atherosclerosis through T cell mediated immune response in apoE (-/-) mice. We also reported that immunization with p210 reduced mean arterial blood pressure (p210 = 124±4*, cBSA = 143±6, PBS = 139±3 mmHg. *p<0.05 vs cBSA and PBS.) and aneurysm formation in AngII-infused apoE (-/-) mice. In this study, we assessed the effect of p210 vaccine on AngII-induced renal inflammatory responses in apoE (-/-) mice.
Method and Results: ApoE (-/-) mice were immunized with p210/cBSA/Alum (p210; 100 μ 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. Serum creatinine level was significantly lower in p210 group (p210 = 0.7±0.1*, cBSA = 1.1±0.1, PBS = 1.4±0.1 mg/dL. N=12, 11, and 9 respectively; *p<0.05 vs cBSA and PBS.). IL-6 and monocyte chemotactic protein-1 (MCP-1) mRNA expression in kidneys were significantly down-regulated in p210 group (IL-6: cBSA = 4.1±1.1, PBS = 3.9±1.0 -fold increase compared to p210; MCP-1: cBSA = 2.4±0.6, PBS = 2.2±0.4 -fold increase compared to p210, N=8). Renal glomerular superoxide production measured by in situ dihydroethidium was significantly decreased in p210 group (cBSA = 3.8±0.7, PBS = 3.9±0.6 -fold increase compared to p210, N=4.). The expression of NOX1, a component of NADPH oxidase, mRNA in kidneys was significantly down-regulated in p210 group (cBSA = 2.6±0.5, PBS = 2.8±0.4 -fold increase compared to p210, N=8.).
Conclusion: Immunization with p210 significantly attenuated AngII-induced renal damage. These anti-hypertensive and renal protective effects were associated with down-regulation of IL-6 and MCP-1 expression, and ROS production mediated by NADPH oxidase in kidneys.
- © 2012 by American Heart Association, Inc.