Abstract 12741: Prevention of Aneurysm Progression by a Peptide Vaccine Against Angiotensin II in a Rat Model

• Published in: Circulation (New York, N.Y.) Vol. 140; no. Suppl_1 Suppl 1; p. A12741
• Main Authors: Kurashiki, Tomohiro, Miyake, Takashi, Nakagami, Hironori, Nishimura, Motonobu, Morishita, Ryuichi
• Format: Journal Article
• Language: English
• Published: by the American College of Cardiology Foundation and the American Heart Association, Inc 19-11-2019
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.140.suppl_1.12741

Abdominal aortic aneurysm (AAA) is a common degenerative condition with high mortality in elderly individuals. However, there is no proven medical therapy to inhibit AAA progression in the clinical setting. To develop a novel therapeutic approach for treating AAA, we focused on vaccination targeting Angiotensin II (Ang II). Ang II is thought to participate in aneurysm formation, because of its ability to induce inflammation in the aortic wall. Therefore, we assessed the hypothesis that Ang II antibody elicited by the Ang II vaccine could exert a long-lasting anti-inflammatory effect in the AAA wall, leading to a potent therapeutic effect on aneurysm progression. Ang II peptide was conjugated with keyhole limpet hemocyanin (KLH) carrier protein to induce sufficient immune response. Male rats were subcutaneously immunized with Ang II-KLH (20ug/time) with an adjuvant (aluminum hydroxide) on days 0, 14, and 28. Aortic dilatation was induced by intraluminal incubation with elastase for 30 minutes on day 35. The injection of Ang II vaccines effectively induced production of high titer of anti-Ang II antibodies, and the presence of anti-Ang II antibodies were detected at least 9 weeks after vaccination, whereas it was negligible in unimmunized rats. Ultrasound analysis demonstrated that immunization with the Ang II vaccine significantly inhibited the expansion of experimental AAA compared with control subjects (n=6 per group, Control 6.13±2.16 mm, Ang II vaccine 3.65±0.81 mm, P<0.01), independent of its blood pressure-lowering effect. Four weeks after operation, an increase in concentration of Ang II in the aneurysm wall was significantly suppressed by treatment with Ang II vaccine. Immunization with the Ang II vaccine suppressed accumulation of macrophages and CD4 T-cells, leading to inhibition of expression of TNF-α and IL-1β. In addition, activation of MMP-2 and MMP-9 was also suppressed by immunization with the Ang II vaccine, resulted in protection against destruction of elastic fibers. In conclusion, immunization with Ang II vaccine resulted in induction of specific antibodies, leading to prevention of AAA progression through anti-inflammatory effects. This vaccine could become a potent therapeutic option for treating patients with AAA.