Acid ceramidase gene therapy ameliorates pulmonary arterial hypertension with right heart dysfunction.

ABSTRACT:

Background

Up-regulation of ceramides in pulmonary hypertension (PH), contributing to perturbations in sphingolipid homeostasis and the transition of cells to a senescence state. We assessed the safety, feasibility, and efficiency of acid ceramidase gene transfer in a rodent PH model.

Methods

A model of PH was established by the combination of left pneumonectomy and injection of Sugen toxin. Magnetic resonance imaging and right heart catheterization confirmed development of PH. Animals were subjected to intratracheal administration of synthetic adeno-associated viral vector (Anc80L65) carrying the acid ceramidase (Anc80L65.AC), an empty capsid vector, or saline. Therapeutic efficacy was evaluated 8 weeks after gene delivery.

Results

Hemodynamic assessment 4 weeks afte

SUBMITTER: Katz MG 

PROVIDER: S-EPMC10416391 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature