The novel sphingosine-1-phosphate receptor modulator KRP-203 prevents myocardial ischemia-reperfusion injury by preserving mitochondrial function through activation of the RISK and SAFE signaling pathways.

ABSTRACT: KRP-203, a novel agonist of sphingosine-1-phosphate receptors (S1PRs), has shown promise in treating in immune-related diseases by blocking lymphocyte recruitment to inflamed tissues. Although S1PRs are abundantly expressed in cardiomyocytes, the specific effects of KRP-203 on these cells remain poorly understood. Here, we investigated the impact and mechanisms of KRP-203 pretreatment on myocardial ischemia-reperfusion injury (MIRI) via its interaction with cardiomyocyte S1PRs. To evaluate the efficacy of KRP-203 administered before ischemia, three MIRI models (in vivo, ex vivo, and in vitro) were employed. Overall, KRP-203 pretreatment significantly improved left ventricular systolic function, lowered serum levels of creatine kinase MB isoenzyme and lactate dehydrogenase, mitigated myocar

SUBMITTER: Wu N 

PROVIDER: S-EPMC12660407 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature