Exosomal lncRNA PVT1 from adipose-derived stem cell aggravates myocardial injury through CDC25A/PI3Kγ/NF-κB pathway under high glucose condition

Diabetic cardiomyopathy (DCM) is an important cardiovascular complication of diabetes. However, the pathogenesis of myocardial injury in DCM is still unclear. In-depth exploration of the pathogenesis of myocardial injury in DCM is helpful for drug target screening and clinical treatment of DCM. Adipose-derived stem cells (ADSCs) contribute to cardiovascular disease by transferring exosomal long noncoding RNAs (lncRNAs). Nevertheless, the role of exosomal lncRNA PVT1 oncogene (PVT1) derived from ADSCs in myocardial injury of DCM remains unknown. An in-vitro high glucose (HG) model consisting of cultured human ADSCs and AC16 cardiomyocyte-like cells was used in this study, and AC16 cells were incubated with exosomes derived from ADSCs. Besides, methylation of PVT1 was identified by Methylated RNA Immunoprecipitation (MeRIP), and RNA antisense purification (RAP) was performed to explore lncRNA-mRNA interaction. Herein, the current study indicates that HG increases PVT1 level in ADSCs and exosomes derived from ADSCs by improving m 6 A modification of PVT1. Besides, ADSCs aggravate myocardial injury by delivering exosomal PVT1 to cardiomyocytes under HG condition. Mechanistically, exosomal PVT1 derived from ADSCs enhances myocardial injury through cell division cycle 25A (CDC25A) by enhancing nuclear factor kappa B (NF-κB)-associated signaling via suppressing phosphoinositide 3-kinase gamma (PI3Kγ) under HG condition. The identified pathway represents a candidate molecular mechanism for further investigation rather than clinically validated therapeutic targets for DCM.