A Prostacycline Analog Prevents Chronic Myocardial Remodeling in Murine Cardiac Allografts

Abstract

SummaryONO-1301MS is a compound that acts as a prostacyclin agonist with thromboxane A2 synthase inhibitory activity. We investigated the effect of ONO-1301MS on myocardial remodeling in murine cardiac allografts. The hearts of Balb/c mice were transplanted into C3H/He mice (a full allomismatch combination) to assess acute rejection or C57BL/6 hearts into B6.C-H2 <bm12> KhEg (a class II mismatch combination) to examine chronic rejection. ONO-1301MS did not prolong full allomismatch cardiac graft survival. Severe myocardial fibrosis with high collagen concentration was observed in untreated class II mismatch allografts on day 60. However, significantly suppressed myocardial fibrosis with less collagen synthesis was observed in the ONO-1301MS-treated group compared to the control group. ONO-1301MS could be an effective strategy to suppress chronic myocardial remodeling in cardiac transplantation. (Int Heart J 2012; 53: 64-67)

Effect of Prostaglandin I2 Analogs on Macrophage Inflammatory Protein 1α in Human Monocytes via I Prostanoid Receptor and Cyclic Adenosine Monophosphate

“…We here also investigated the effect of the new PGI 2 analog, ONO-1301, on the LPS-induced MIP-1α/CCL3 expression in monocytes to be the guide for clinical selection. 22 However, the suppressive effect of ONO-1301 on the LPS-induced MIP-1α expression in monocytes was not better than other conventional PGI 2 analogs. In the present study, iloprost inhibited the production of MIP-1α production by monocytes from human peripheral blood.…”

A sustained-release drug-delivery system of synthetic prostacyclin agonist, ONO-1301SR: a new reagent to enhance cardiac tissue salvage and/or regeneration in the damaged heart

“…Furthermore, positive effects of ONO-1301SR were shown in other cardiac pathologies such as cardiac graft disease post-transplantation [73] or autoimmune myocarditis.…”

“…Suzuki et al [73] subcutaneously injected ONO-1301SR into the mice that were subjected to heterotopic cardiac allograft transplantation in the aim to test the effects of ONO-1301SR on acute and chronic graft-host disease. This treatment was effective in chronic rejection as shown in the reduced myocardial fibrosis in a class II mismatch combination, but not effective in acute rejection in a full allomismatch combination, suggesting that ONO-1301SR might be a potential new drug for chronic rejection post-cardiac allograft transplantation.…”