Gene Therapy Targeting <i>Pkp2</i> Deficiency Attenuates Cardiac Fibrosis: Insights From Single-Cell Transcriptomics in <i>Pkp2</i>-Knockout Rats.

ABSTRACT: Heart failure (HF), characterized by maladaptive cardiac fibrosis and progressive functional deterioration, remains a therapeutic challenge. In this study, we established a cardiac organoid HF model derived from human-induced pluripotent stem cells (hiPSCs) and observed a significant downregulation of the desmosomal protein plakophilin-2 (PKP2) in this model. Reduced PKP2 expression was detected in both HF rat and mouse. Subsequent in vivo studies on Pkp2-knockout (Pkp2-KO) rats demonstrated that adeno-associated virus serotype 9 (AAV9)-mediated restoration of PKP2 not only restored cardiac PKP2 expression but also attenuated the progression of fibrosis. Administration of AAV9-PKP2 could also inhibit myocardial fibrosis and slow down disease progression in HF mouse. Single-ce

SUBMITTER: Ding X 

PROVIDER: S-EPMC12446705 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature