Rap2a promotes cardiac fibrosis and exacerbates myocardial infarction through the TNIK/Merlin/YAP axis.

Myocardial fibrosis constitutes the primary pathological characteristic of myocardial infarction (MI). The activation and proliferation of myocardial fibroblasts serve as crucial factors in the process of the development of fibrosis in the myocardium. Our research delved into the role that Rap2a plays in cardiac function as well as myocardial fibrosis, while its effects on cardial fibroblasts (CFs) proliferation, migration, and phenotypic transformation were also explored. Examination of the GEO database showed a notable increase in the expression of Rap2a within myocardial tissue from mice with MI compared to normal mice. Rap2a deficiency relieves MI in mice and restrains the phenotypic transition, proliferation, and migration of CFs. The absence of Rap2a mitigates MI in mice. Besides, it curbs the growth of CFs, restricts their movement, and prevents them from undergoing phenotypic conversion. Rap2a can bind to TNIK in myocardial fibroblasts and enhance TNIK expression; Merlin/YAP signaling pathway was assessed as a downstream target of TNIK to further elucidate the regulatory mechanism through which Rap2a influences cardiomyocytes. In conclusion, this study provides evidence that Rap2a promotes myocardial fibrosis through mediating the myofibroblast transformation, proliferation, and migration of CFs via the TNIK/Merlin/YAP pathway, thereby exacerbating symptoms of myocardial infarction.