Chimeric Adeno-Associated Virus-Mediated Cardiovascular Reprogramming for Ischemic Heart Disease.

ACS omega2018PMID: 30023931

View on PubMed DOI: 10.1021/acsomega.8b00904

Plain Language Summary

Tests dual chimeric AAV gene therapy combining cardiac transcription factor reprogramming (Gata4/Mef2c/Tbx5 = GMT vectors) with thymosin β4 for ischemic heart disease. GMT converted cardiac fibroblasts toward cardiomyocyte-like cells while AAV-TB4 promoted regeneration and limited collagen deposition in a synergistic manner. Combined GMT+TB4 gene delivery produced greater cardiac-specific gene expression and reduced fibrosis than either vector alone. Demonstrates TB4 gene therapy as an adjunct to cellular reprogramming—combining direct lineage conversion with pro-regenerative peptide delivery.

Abstract

Here, we demonstrated chimeric adeno-associated virus (chimeric AAV), AAV-DJ-mediated cardiovascular reprogramming strategy to generate new cardiomyocytes and limit collagen deposition in cardiac fibroblasts by inducing synergism of chimeric AAV-expressing Gata4, Mef2c, Tbx5 (AAV-GMT)-mediated heart reprogramming and chimeric AAV-expressing thymosin β4 (AAV-Tβ4)-mediated heart regeneration. AAV-GMT promoted a gradual increase in expression of cardiac-specific genes, including Actc1, Gja1, Myh6, Ryr2, and cTnT, with a gradual decrease in expression of a fibrosis-specific gene, procollagen type I and here AAV-Tβ4 help to induce GMT expression, providing a chimeric AAV-mediated therapeutic cell reprogramming strategy for ischemic heart diseases.

Authors

Yoo, So Young; Jeong, Su-Nam; Kang, Jeong-In; Lee, Seung-Wuk