PS-B03-4: A NOVEL SOLUBLE EPOXIDE HYDROLASE VACCINE PROTECTS MURINE CARDIAC MUSCLE AGAINST MYOCARDIAL INFARCTION

Abstract

Objective: Myocardial infarction is still a life-threatening disease, even though its prognosis has been improved through the development of percutaneous coronary intervention and pharmacotherapy. In addition, heart failure due to remodeling after myocardial infarction requires lifelong management. The aim of this study was to develop a novel treatment suppressing the myocardial damage done by myocardial infarction. Design and method: We focused on inhibition of soluble epoxide hydrolase to prolong the activation of epoxyeicosatrienoic acids (EETs), which have vasodilatory and anti-inflammatory properties. The several amino acid sequence of Soluble Epoxide Hydrolase (sEH) protein was designed as peptide vaccine. The 40 rats were injected the vaccine subcutaneously and the other 30 rats were injected the saline solution and adjuvant four times in every two weeks. The left anterior descending artery was ligated in both groups as myocardial infarction model, and those hearts were evaluated by cardiac echography and cardiac tissue were examined histologically on day7 after the surgery. Results: In the vaccine group, the ischemic area was significantly reduced, and systolic cardiac function was significantly preserved. Vaccine treatment clearly increased microvessels in the border area and suppressed fibrosis in the cardiac tissue secondary to myocardial infarction. Furthermore, VEGF and eNOS expression were upregulated in the cardiac tissue of the vaccine group, suggesting induced EETs caused neovascularization through modifying protein expression. Conclusions: We successfully made a new vaccine to inactivate soluble epoxide hydrolase, and we have evaluated the effect of the vaccine in a rat myocardial infarction model. The soluble epoxide hydrolase vaccine is a novel treatment for improving cardiac function following myocardial infarction.