Effects of antisense peptide nucleic acid to platelet-derived growth factor A-chain on growth of vascular smooth muscle cells

To investigate antisense peptide nucleic acid (PNA) as a gene therapy for the arterial proliferative diseases, the authors designed and examined the effects of an antisense PNA targeting platelet-derived growth factor (PDGF) A-chain on expression of PDGF A-chain and growth of vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats. A 15-mer antisense PNA complementary to the initiation codon of rat and human PDGF A-chain mRNA was synthesized and purified by high-performance liquid chromatography. Gel-shift assay and biomolecular interaction analysis (BIAcore) revealed that the antisense PNA bound weakly to the target RNA, whereas it bound strongly to the target DNA. Fluorescein-isothiocyanate-labeled antisense PNA to PDGF A-chain was taken up slowly and maintained in VSMCs for a prolonged period of time. Antisense PNA inhibited expression of PDGF A-chain mRNA and protein as well as DNA synthesis in VSMCs in a dose-independent manner. Inhibition of DNA synthesis by the antisense PNA was greater than that by the antisense DNA at a low concentration (0.5 μmol/L). These results suggest that antisense PNA to PDGF A-chain will be used as a gene therapy for vascular proliferative diseases such as hypertensive vascular diseases, restenosis of coronary arteries after angioplasty, and atherosclerosis.