410 EFFICACY OF VACCINATION AGAINST THE ANGIOTENSIN II TYPE 1 RECEPTOR AND APOB100 FOR THE PREVENTION OF ATHEROSCLEROSIS

Objectives: Atherosclerosis is a major cause of cardiovascular morbidity and mortality, therefore new methods for atherosclerosis prevention are required. The aim of this study was to evaluate the effects of an Ang II type 1 (AT1) receptor vaccine and ApoB100 vaccine on atherosclerosis and hyperlipidemia-related nephropathy. Methods: Peptide sequences from the AT1 receptor or ApoB100, were synthesized and coupled to the carrier protein keyhole limpet haemocyanin (KLH). Male spontaneously hyperlipidemic (SHL) mice (n = 60) were treated transiently with three injections of vehicle, AT1 receptor vaccine (0.02 mg) or ApoB100 vaccine (0.05 mg) at age 4, 6 and 8 weeks, or continuously with candesartan cilexetil (1 mg/kg/day). SHL mice were given a high fat diet and 1% NaCl in the drinking water to induce atherosclerosis and glomerular lipid deposition. Atherosclerotic lesions were measured by Sudan IV stain positive areas of aorta and glomerular lesions by Oil-red-O stain positive area. Results: Vaccination against the AT1 receptor and ApoB100 did not cause a significant change in serum lipids or blood pressure. Atherosclerotic lesions and albuminuria were significantly suppressed by vaccination against the AT1 receptor, as well as by continuous treatment with candesartan, and a similar trend was seen for glomerular lipid deposition. However, vaccination against ApoB100 did not cause a significant suppression of the atherosclerotic area or glomerular lesions. Conclusion: AT1 receptor vaccination may be effective for the attenuation of atherosclerosis and hyperlipidemia-related nephropathy. In contrast, ApoB100 vaccination was not found to be effective for prevention of atherosclerosis in this model of atherosclerosis.