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Updated: May 24, 2026
Surgical Porcine Model of Chronic Myocardial Ischemia Treated by Exosome-laden Collagen Patch and Off-pump Coronary Artery Bypass Graft
Published on: September 15, 2023
A prostacycline analog prevents chronic myocardial remodeling in murine cardiac allografts
Jun-ichi Suzuki1, Masahito Ogawa, Yoshiki Sakai
1Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Abstract:
ONO-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.
Insights
ONO-1301MS, a prostacyclin agonist, did not prevent acute cardiac allograft rejection but significantly reduced myocardial fibrosis in chronic rejection models. This compound shows promise for managing long-term cardiac transplant complications.
Area of Science:
- Cardiovascular Research
- Immunology
- Pharmacology
Background:
- Myocardial remodeling and fibrosis are significant challenges in cardiac transplantation.
- Prostacyclin agonists and thromboxane A2 synthase inhibitors are potential therapeutic targets.
Purpose of the Study:
- To investigate the efficacy of ONO-1301MS in mitigating myocardial remodeling in murine cardiac allografts.
- To assess the impact of ONO-1301MS on acute and chronic rejection pathways.
Main Methods:
- Murine cardiac allograft models were established using full allomismatch and class II mismatch combinations.
- ONO-1301MS treatment was administered to assess its effects on graft survival and myocardial fibrosis.
- Collagen concentration was quantified to evaluate fibrosis severity.
Main Results:
- ONO-1301MS did not extend survival in the acute rejection model (full allomismatch).
- Significant suppression of myocardial fibrosis and collagen synthesis was observed in ONO-1301MS-treated class II mismatch allografts.
- Untreated class II mismatch allografts exhibited severe myocardial fibrosis.
Conclusions:
- ONO-1301MS demonstrates potential in suppressing chronic myocardial remodeling in cardiac transplantation.
- The compound may be a viable strategy for managing fibrosis post-transplant.
- Further research is warranted to explore its therapeutic application in chronic allograft dysfunction.
