GMRSP encoded by lncRNA H19 regulates metabolic reprogramming and alleviates aortic dissection.

ABSTRACT: Metabolic disturbances are hallmarks of vascular smooth muscle cell (VSMC) phenotypic transitions, which play a critical role in the pathogenesis of aortic dissection (AD). In this study, we identify and characterize glucose metabolism regulatory protein (GMRSP), a protein encoded by lncRNA H19. Using VSMC-specific GMRSP induction in knock-in mice, adeno-associated virus-mediated GMRSP overexpression, and exosomal GMRSP delivery, we demonstrate significant improvements in AD and mitochondrial dysfunction. Mechanistically, GMRSP inhibits heterogeneous nuclear ribonucleoprotein (hnRNP) A2B1-mediated alternative splicing of pyruvate kinase M (PKM) pre-mRNA, leading to reduced PKM2 production and glycolysis. This reprogramming preserves the contractile phenotype of VSMCs and prevents their tra

SUBMITTER: Wang J 

PROVIDER: S-EPMC11836370 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature