Adenovirus-mediated transfer of ribozyme targeting platelet-derived growth factor A-chain mRNA inhibits growth of vascular smooth muscle cells from spontaneously hypertensive rats.

Abstract

Platelet-derived growth factor (PDGF) is a potent stimulator of growth of vascular smooth muscle cells (VSMCs). VSMCs from spontaneously hypertensive rats (SHRs) show exaggerated growth and increasingly express PDGF A-chain messenger RNA (mRNA). To examine adenovirus-mediated transfer of a ribozyme targeting the PDGF A-chain mRNA as a possible gene therapy for vascular proliferative diseases, a recombinant adenovirus vector encoding a ribozyme that targets rat PDGF A-chain mRNA (Ad. ribozyme) was designed and synthesized and its effect on the growth of VSMCs from SHRs was investigated. This vector dose-dependently inhibited DNA synthesis in VMSCs from SHRs, whereas an adenovirus vector encoding the Escherichia coli LacZ gene (Ad. LacZ) did not affect DNA synthesis. Ad. ribozyme significantly suppressed proliferation of VSMCs from SHRs in a dose-dependent manner. Ad. LacZ had no effect. Ad. ribozyme significantly inhibited expression of PDGF A-chain mRNA and PDGF-AA protein in VSMCs from SHRs. Ad. LacZ had no effect. These results demonstrated that adenovirus-mediated transfer of a ribozyme targeting the PDGF A-chain mRNA effectively and specifically inhibited the growth of VSMCs from SHRs with suppression of PDGF A-chain mRNA and PDGF-AA protein expression. Adenovirus-mediated transfer of ribozyme targeting PDGF A-chain mRNA may be a feasible gene therapy for vascular proliferative diseases.