Background: Cold-induced RNA binding protein (CIRBP) is widely involved in critical physiological processes of myocardial fibrosis (MF), a crucial mechanism of cardiac insufficiency in myocardial infarction (MI). However, whether CIRBP affect MF in MI patients after ECMO is unclear. Our study aims to investigate the effect of ECMO on MF after MI and explore its possible mechanism.

Methods: In our study, we developed ECMO and MI rat models to explore ECMO’s effect on MF. Thirty rats were divided into four groups: Control, ECMO, MI, and MI+ECMO, with a 28-day observation period. We assessed collagen deposition using cardiac echocardiography, Masson’s trichrome, TTC staining, and measured α-SMA. Integrating transcriptomics and proteomics, we focused on the CIRBP protein’s role. CO-IP and RIP helped identify key downstream molecules and their functions.

Results: After the successful establishment of rat models for ECMO and MI, echocardiographic analysis revealed a marked decrease in cardiac function in the ECMO+MI. A series of histological assessments indicated an exacerbation of MF post-ECMO. Transcriptomic and proteomic identified the critical protein CIRBP which elevates in the serum of both patients and rat models following ECMO exposureFurther investigative techniques elucidated CIRBP interact with P4HB, thereby fostering collagen production.

Conclusions: In conclusion, ECMO post-MI contribute to the exacerbation of MF. This effect is likely linked to the increased synthesis of CIRBP, in conjunction with P4HB, leads to an overproduction of collagen. Hence, targeting CIRBP could be an effective strategy to alleviate this adverse effect, pointing towards a novel therapeutic direction in post-MI treatment.